How plasma cells develop. Deutsches Rheuma Forschungs Zentrum, Berlin Institut der Leibniz Gemeinschaft

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "How plasma cells develop. Deutsches Rheuma Forschungs Zentrum, Berlin Institut der Leibniz Gemeinschaft"

Transcription

1 How plasma cells develop Deutsches Rheuma Forschungs Zentrum, Berlin Institut der Leibniz Gemeinschaft 1

2 Plasma cells develop from activated B cells Toll Like Receptor B Cell Receptor B cell B cell microbia antigen specific 2

3 plasma blast plasma cell Pre-Plasmablast Plasmablast Plasma cell IgG DAPI membrane Ig > secreted Ig mig <<< secreted Ig 3

4 Immune response Naive B cell Peripheral lymphoid organs Memory B cell Germinal center IgM Pasma cell Plasma cells T cell - independent T cell - dependent 4

5 Germinal center reaction clonal expansion Ig class switch affinity maturation establishment of the memory compartment 5

6 U Germinal center reaction U U Y Memory B cell Y Y Y Y Y Plasma cells Antigen Proliferation Hypermutation Selection Differentiation Dark zone Light zone 6

7 Affinity maturation A. Hypermutation B. Selection 1. follicular dendritic cell (FDC) 2. T -follicular helper cell (TFh) 7

8 Hypermutation highly specific mechanism nucleotide exchanges are introduced at a high rate of 10-3 / base pairs / generation accumulate specifically in the rearranged V- region genes active for a short time period 8

9 Selection Follicular dendritic cells T FDC support B cell B homeostasis affinity maturation Lymphoid follicle 9

10 Follicular dendritic cells: non hematopoietic cells antigen-antibody complexes bound to the surface present antigen to B cells 10

11 Suzuki K, Cyster J. JEM

12 Follicular dendritic cells: secrete the chemokine CXCL13 CCR7 T B CXCR5 12

13 T follicular helper cells Reticular cells CCL19 / CCL21 T cell zone Nutt and Tarlinton 13

14 Affinity selected differentiation IL-21 IL-21R T FH ICOS CD40L TCR ICOSL CD40 class II B GC CXCR5 antigen BAFF CXCR5 CXCL13 FDC CXCL13 14

15 development of plasma cells secreting antibodies of high affinity takes place in germinal centers 15

16 Transcription factors controlling the development of plasma cells B defines: Pax5 B cell state Blimp 1 B lymphocyte induced maturation protein 1 transcriptional repressor Plasma cell state regulate mutually exclusive transcriptional programs 16

17 Network of TF regulating the development of plasma cells maintain B cell phenotype: Pax5, Bach2 and Bcl6, promote plasma cell differentiation: Irf4, Blimp1 and Xbp1 B cell Plasma celle Germinal center B cell 17

18 UPR - unfolding protein response ER nucleus stress sensors: Ire1 induces splicing of Xbp1 ER stress Atf6 activation of ER chaperones folding enzymes Stress response expansion of the ER burden of unfolded protein increasing protein processing capacity enhanced secretion of Ig 18

19 XBP-1 is required for high Ig secretion XBP-1 deficient B cells Nutt SL JI 19

20 Persistent serum antibody titer 16 years 20 years Amanna and Slifka 2010

21 Induction selection Persistent serum antibody titer homeostasis serum antibody magnitude splenic plasma cells days months and years short lived plasma cells Slifka and Ahmed 1998 Manz et al,

22 Persistent serum antibdy titer How is that achieved? Memory B cells Plasma cells 22

23 Twoarmsofmemory Memory B cell Memory plasma cell Immune response to small pocks 23

24 Long-term maintenance of plasma cells Induction selection homeostasis serum antibody magnitude bone marrow plasma cells splenic plasma cells days short lived plasma cells long lived plasma cells months and years Slifka and Ahmed 1998 Manz et al,

25 25

26 Development of long-lived plasma cells Naive B cell Peripheral lymphoid organs Germinal center Memory B cell IgM Pasma cell Long lived plasma cells 26

27 Migration of plasma cells to the bone marrow Stromal cell Bone marrow CXCR4 CXCL12 Benner at el, 1981 Hauser et al, 2003 Chu et al,

28 Peripheral lymphoid organs Bone marrow Tokoyoda et al, 2004 network of Follicular Dendritic Cells bone marrow stromal cell Lymphocytes are attracted by the chemokine CXCL13 Plasma cells are attracted by the chemokine CXCL12 B cells are embedded in a network of FDC Plasma cells are in contact with stromal cells 28

29 Bone marrow survival niche APRIL IL-6 Plasma cell? Stromal cell CXCR4 CXCL12 29

30 Plasma cell survival factors Ligand APRIL IL-6 BAFF IL-5 TNF-α IL-10 Receptors TACI, BCMA, PGL IL-6R BAFF-R, TACI, BCMA IL-5R TNF-Rs IL-10R Cassese et al,

31 BAFF and APRIL belong to TNF superfamily 31

32 Molecular basis of plasma cell survival Tumor necrosis super family BAFF BAFF-R B cell APRIL BCMA TACI plasma cells myeloid cell B cell plasma cell MacKay et al

33 BAFF BAFF APRIL B cell plasma blast plasma cell BAFF -R BCMA O Connor et al, Belnoue et al, 2008

34 In the bone marrow F4/80 GR-1 lo cells produce APRIL 9.02% 8.89 % Gr-1 F4/80 I-APRIL Chu et al,

35 Macrophages and eosinophils produce APRIL and Il-6 Eosinophils R2 eosinophils R1 33% R2 17% eosinophil precursors SSC CD11b R3 46% monocytes/macrophages R3 35

36 APRIL and IL-6 is found in the granules of Eos APRIL MBP IL-6 MBP MBP - Major Basic Protein Deutsches Rheuma Forschungs 36 Zentrum, Berlin

37 Eosinophils support plasma cell survival by secretion of APRIL and IL % of Max _ Annexin-V TACI-Ig anti-il-6 37

38 Development of mature long lived plasma cells 38

39 The plasma cell survival niche Stromal cells eosinophils plasma cell 30 µm section Chu Van Trung 39

40 Plasma cell survival is dependent on Eosinophils 1 ip 2 ip. BALB/c Naive 6 weeks d 0 2 months d 60 Day 60 1 week 3 injections with Siglec F specific antibody 40

41 CD138 hi plasma cells RatIgG2a α-siglec-f BM Spleen % of Max Annexin-V Deutsches Rheuma Forschungs 41 Zentrum, Berlin

42 How plasma cells develop plasma cells develop from antigen activated B cells their development is dependent on the TF BLIMP-1 the germinal center reaction is a pre-requisite for the generation of long-lived plasma cells eosinophils are required for the establishment and the maintenance of the plasma cell survival niche 42

43 Deutsches Rheuma Forschungs Zentrum, Berlin Institut der Leibniz Gemeinschaft 43

B cell activation and antibody production. Abul K. Abbas UCSF

B cell activation and antibody production. Abul K. Abbas UCSF 1 B cell activation and antibody production Abul K. Abbas UCSF 2 Lecture outline B cell activation; the role of helper T cells in antibody production Therapeutic targeting of B cells 3 Principles of humoral

More information

Helper-T-cell regulated B-cell differentiation. Phase I begins at the site of infection with acute inflammation that leads to the activation and

Helper-T-cell regulated B-cell differentiation. Phase I begins at the site of infection with acute inflammation that leads to the activation and 1 2 Helper-T-cell regulated B-cell differentiation. Phase I begins at the site of infection with acute inflammation that leads to the activation and emigration of DCs to the T- cell zones of the lymph

More information

Eosinophils are required. for the maintenance of plasma cells in the bone marrow

Eosinophils are required. for the maintenance of plasma cells in the bone marrow Eosinophils are required for the maintenance of plasma cells in the bone marrow Van Trung Chu, Anja Fröhlich, Gudrun Steinhauser, Tobias Scheel, Toralf Roch, Simon Fillatreau, James J. Lee, Max Löhning

More information

Introduction. Abbas Chapter 10: B Cell Activation and Antibody Production. General Features. General Features. General Features

Introduction. Abbas Chapter 10: B Cell Activation and Antibody Production. General Features. General Features. General Features Introduction Abbas Chapter 10: B Cell Activation and Antibody Production January 25, 2010 Children s Mercy Hospitals and Clinics Humoral immunity is mediated by secreted antibodies (Ab) Ab function to

More information

Normal GC initiation then collapse; normal mutation and 10. Constitutive signalling leads to spontaneous GC in PP, even BCR -/- 19

Normal GC initiation then collapse; normal mutation and 10. Constitutive signalling leads to spontaneous GC in PP, even BCR -/- 19 S1 Genetic modifications affecting germinal-centre formation and function Gene Compartment GC Phenotype Ref LTα, LTβ, TNF, Organ Disorganized lymphoid architecture in spleens; poor 1 TNFRI, LTβR architecture

More information

REQUIREMENTS FOR MEMORY B CELL AND LONG LIVED PLASMA CELL DEVELOPMENT DURING ADAPTIVE IMMUNE RESPONSES AND STAPHYLOCOCCUS AUREUS INFECTION

REQUIREMENTS FOR MEMORY B CELL AND LONG LIVED PLASMA CELL DEVELOPMENT DURING ADAPTIVE IMMUNE RESPONSES AND STAPHYLOCOCCUS AUREUS INFECTION REQUIREMENTS FOR MEMORY B CELL AND LONG LIVED PLASMA CELL DEVELOPMENT DURING ADAPTIVE IMMUNE RESPONSES AND STAPHYLOCOCCUS AUREUS INFECTION Amanda Beth Keener A dissertation submitted to the faculty at

More information

MECHANISMS OF CELLULAR REJECTION IN ORGAN TRANSPLANTATION AN OVERVIEW

MECHANISMS OF CELLULAR REJECTION IN ORGAN TRANSPLANTATION AN OVERVIEW MECHANISMS OF CELLULAR REJECTION IN ORGAN TRANSPLANTATION AN OVERVIEW YVON LEBRANCHU Service Néphrologie et Immunologie Clinique CHU TOURS ANTIGEN PRESENTING CELL CD4 + T CELL CYTOKINE PRODUCTION CLONAL

More information

Immunology 2017: Lecture 12 handout. Secondary lymphoid organs. Dr H Awad

Immunology 2017: Lecture 12 handout. Secondary lymphoid organs. Dr H Awad Immunology 2017: Lecture 12 handout Secondary lymphoid organs Dr H Awad INTRODUCTION So far we discussed the cells of the immune system and how they recognize their antigens and get stimulated. The number

More information

Immunopathogenesis of SLE and Rationale for Biologic Therapy

Immunopathogenesis of SLE and Rationale for Biologic Therapy Immunopathogenesis of SLE and Rationale for Biologic Therapy Peter Lipsky, MD Editor, Arthritis Research and Therapy Bethesda, MD Environmental Triggers, Gender, and Genetic Factors Contribute to SLE Pathogenesis

More information

Effector T Cells and

Effector T Cells and 1 Effector T Cells and Cytokines Andrew Lichtman, MD PhD Brigham and Women's Hospital Harvard Medical School 2 Lecture outline Cytokines Subsets of CD4+ T cells: definitions, functions, development New

More information

Lymphoid Organs and Lymphocyte Trafficking. Dr. Issa Abu-Dayyeh

Lymphoid Organs and Lymphocyte Trafficking. Dr. Issa Abu-Dayyeh Lymphoid Organs and Lymphocyte Trafficking Dr. Issa Abu-Dayyeh Invader recognition Where does invader recognition take place?? Secondary lymphoid organs: Lymph nodes Spleen Mucosal-associated lymphoid

More information

ACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS. Choompone Sakonwasun, MD (Hons), FRCPT

ACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS. Choompone Sakonwasun, MD (Hons), FRCPT ACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS Choompone Sakonwasun, MD (Hons), FRCPT Types of Adaptive Immunity Types of T Cell-mediated Immune Reactions CTLs = cytotoxic T lymphocytes

More information

The role of T-cell B-cell interations in germinal center reactions in Rheumatoid Arthritis

The role of T-cell B-cell interations in germinal center reactions in Rheumatoid Arthritis The role of T-cell B-cell interations in germinal center reactions in Rheumatoid Arthritis 15-03-2011 Veerle Huijgen Master Thesis The role of T-cell B-cell interactions in germinal center reactions in

More information

TCR, MHC and coreceptors

TCR, MHC and coreceptors Cooperation In Immune Responses Antigen processing how peptides get into MHC Antigen processing involves the intracellular proteolytic generation of MHC binding proteins Protein antigens may be processed

More information

Acquired Immunity 2. - Vaccines & Immunological Memory - Wataru Ise. WPI Immunology Frontier Research Center (IFReC) Osaka University.

Acquired Immunity 2. - Vaccines & Immunological Memory - Wataru Ise. WPI Immunology Frontier Research Center (IFReC) Osaka University. Acquired Immunity 2 - Vaccines & Immunological Memory - Wataru Ise WPI Immunology Frontier Research Center (IFReC) Osaka University Outline 1. What is vaccine (vaccination)? 2. What is immunological memory?

More information

Antigen-Independent B-Cell Development Bone Marrow

Antigen-Independent B-Cell Development Bone Marrow Antigen-Independent B-Cell Development Bone Marrow 1. DNA rearrangements establish the primary repertoire, creating diversity 2. Allelic exclusion ensures that each clone expresses a single antibody on

More information

The generation of antibody-secreting plasma cells

The generation of antibody-secreting plasma cells REVIEWS The generation of antibody-secreting plasma cells Stephen L. Nutt, Philip D. Hodgkin, David M. Tarlinton and Lynn M. Corcoran Abstract The regulation of antibody production is linked to the generation

More information

IMMUNOLOGICAL MEMORY. CD4 T Follicular Helper Cells. Memory CD8 T Cell Differentiation

IMMUNOLOGICAL MEMORY. CD4 T Follicular Helper Cells. Memory CD8 T Cell Differentiation IMMUNOLOGICAL MEMORY CD4 T Follicular Helper Cells Memory CD8 T Cell Differentiation CD4 T Cell Differentiation Bcl-6 T-bet GATA-3 ROR t Foxp3 CD4 T follicular helper (Tfh) cells FUNCTION Provide essential

More information

B Cell Activation and the Humoral Immune Response. Micro 204. Molecular and Cellular Immunology 2013 Lecturer: Jason Cyster

B Cell Activation and the Humoral Immune Response. Micro 204. Molecular and Cellular Immunology 2013 Lecturer: Jason Cyster B Cell Activation and the Humoral Immune Response Micro 204. Molecular and Cellular Immunology 2013 Lecturer: Jason Cyster Vaccine Quest Vaccines are needed that induce broadly neutralizing antibodies

More information

Examples of questions for Cellular Immunology/Cellular Biology and Immunology

Examples of questions for Cellular Immunology/Cellular Biology and Immunology Examples of questions for Cellular Immunology/Cellular Biology and Immunology Each student gets a set of 6 questions, so that each set contains different types of questions and that the set of questions

More information

B Cell Activation and the Humoral Immune Response. Micro 204. Molecular and Cellular Immunology 2012 Lecturer: Jason Cyster

B Cell Activation and the Humoral Immune Response. Micro 204. Molecular and Cellular Immunology 2012 Lecturer: Jason Cyster B Cell Activation and the Humoral Immune Response Micro 204. Molecular and Cellular Immunology 2012 Lecturer: Jason Cyster Constitutive BCR signaling is necessary for B cell survival V-region IgM constant-region

More information

Factors Regulating Immunoglobulin Production by Normal and Disease-Associated Plasma Cells

Factors Regulating Immunoglobulin Production by Normal and Disease-Associated Plasma Cells Biomolecules 2015, 5, 20-40; doi:10.3390/biom5010020 Review OPEN ACCESS biomolecules ISSN 2218-273X www.mdpi.com/journal/biomolecules/ Factors Regulating Immunoglobulin Production by Normal and Disease-Associated

More information

Follicular Lymphoma. ced3 APOPTOSIS. *In the nematode Caenorhabditis elegans 131 of the organism's 1031 cells die during development.

Follicular Lymphoma. ced3 APOPTOSIS. *In the nematode Caenorhabditis elegans 131 of the organism's 1031 cells die during development. Harvard-MIT Division of Health Sciences and Technology HST.176: Cellular and Molecular Immunology Course Director: Dr. Shiv Pillai Follicular Lymphoma 1. Characterized by t(14:18) translocation 2. Ig heavy

More information

Defensive mechanisms include :

Defensive mechanisms include : Acquired Immunity Defensive mechanisms include : 1) Innate immunity (Natural or Non specific) 2) Acquired immunity (Adaptive or Specific) Cell-mediated immunity Humoral immunity Two mechanisms 1) Humoral

More information

Generation of post-germinal centre myeloma plasma B cell.

Generation of post-germinal centre myeloma plasma B cell. Generation of post-germinal centre myeloma. DNA DAMAGE CXCR4 Homing to Lytic lesion activation CD38 CD138 CD56 Phenotypic markers Naive Secondary lymphoid organ Multiple myeloma is a malignancy of s caused

More information

Immune Regulation and Tolerance

Immune Regulation and Tolerance Immune Regulation and Tolerance Immunoregulation: A balance between activation and suppression of effector cells to achieve an efficient immune response without damaging the host. Activation (immunity)

More information

κ λ Antigen-Independent B-Cell Development Bone Marrow Ordered Rearrangement of Ig Genes During B-Cell Development in the Bone Marrow

κ λ Antigen-Independent B-Cell Development Bone Marrow Ordered Rearrangement of Ig Genes During B-Cell Development in the Bone Marrow Antigen-Independent B-Cell Development Bone Marrow 1. DNA rearrangements establish the primary repertoire, creating diversity 2. Allelic exclusion ensures that each clone expresses a single antibody on

More information

The Adaptive Immune Response. B-cells

The Adaptive Immune Response. B-cells The Adaptive Immune Response B-cells The innate immune system provides immediate protection. The adaptive response takes time to develop and is antigen specific. Activation of B and T lymphocytes Naive

More information

Chapter 2 (pages 22 33): Cells and Tissues of the Immune System. Prepared by Kristen Dazy, MD, Scripps Clinic Medical Group

Chapter 2 (pages 22 33): Cells and Tissues of the Immune System. Prepared by Kristen Dazy, MD, Scripps Clinic Medical Group Allergy and Immunology Review Corner: Cellular and Molecular Immunology, 8th Edition By Abul K. Abbas, MBBS; Andrew H. H. Lichtman, MD, PhD; and Shiv Pillai, MBBS, PhD. Chapter 2 (pages 22 33): Cells and

More information

REVIEWS. Dynamics of B cells in germinal centres

REVIEWS. Dynamics of B cells in germinal centres FOCUS ON 50 years of B cells REVIEWS Dynamics of B cells in germinal centres Nilushi S. De Silva and Ulf Klein Abstract Humoral immunity depends on the germinal centre (GC) reaction during which somatically

More information

Innate immunity (rapid response) Dendritic cell. Macrophage. Natural killer cell. Complement protein. Neutrophil

Innate immunity (rapid response) Dendritic cell. Macrophage. Natural killer cell. Complement protein. Neutrophil 1 The immune system The immune response The immune system comprises two arms functioning cooperatively to provide a comprehensive protective response: the innate and the adaptive immune system. The innate

More information

Immunobiology 7. The Humoral Immune Response

Immunobiology 7. The Humoral Immune Response Janeway Murphy Travers Walport Immunobiology 7 Chapter 9 The Humoral Immune Response Copyright Garland Science 2008 Tim Worbs Institute of Immunology Hannover Medical School 1 The course of a typical antibody

More information

Adaptive immune responses: T cell-mediated immunity

Adaptive immune responses: T cell-mediated immunity MICR2209 Adaptive immune responses: T cell-mediated immunity Dr Allison Imrie allison.imrie@uwa.edu.au 1 Synopsis: In this lecture we will discuss the T-cell mediated immune response, how it is activated,

More information

Adaptive Immunity: Humoral Immune Responses

Adaptive Immunity: Humoral Immune Responses MICR2209 Adaptive Immunity: Humoral Immune Responses Dr Allison Imrie 1 Synopsis: In this lecture we will review the different mechanisms which constitute the humoral immune response, and examine the antibody

More information

Mechanisms of anti-sm B cell activation in autoimmune Fas-deficient mice

Mechanisms of anti-sm B cell activation in autoimmune Fas-deficient mice Mechanisms of anti-sm B cell activation in autoimmune Fas-deficient mice Kara Lynne Conway A dissertation submitted to the faculty of the University of North Carolina at Chapel Hill in partial fulfillment

More information

Prepared by Cyrus H. Nozad, MD, University of Tennessee and John Seyerle, MD, Ohio State University

Prepared by Cyrus H. Nozad, MD, University of Tennessee and John Seyerle, MD, Ohio State University Allergy and Immunology Review Corner: Chapter 21 of Middleton s Allergy Principles and Practice, Seventh Edition, edited by N. Franklin Adkinson, et al. Chapter 21: Antigen-Presenting Dendritic Cells (Pages

More information

Andrea s SI Session PCB Practice Test Test 3

Andrea s SI Session PCB Practice Test Test 3 Practice Test Test 3 READ BEFORE STARTING PRACTICE TEST: Remember to please use this practice test as a tool to measure your knowledge, and DO NOT use it as your only tool to study for the test, since

More information

Question 1. Kupffer cells, microglial cells and osteoclasts are all examples of what type of immune system cell?

Question 1. Kupffer cells, microglial cells and osteoclasts are all examples of what type of immune system cell? Abbas Chapter 2: Sarah Spriet February 8, 2015 Question 1. Kupffer cells, microglial cells and osteoclasts are all examples of what type of immune system cell? a. Dendritic cells b. Macrophages c. Monocytes

More information

T Cell Effector Mechanisms I: B cell Help & DTH

T Cell Effector Mechanisms I: B cell Help & DTH T Cell Effector Mechanisms I: B cell Help & DTH Ned Braunstein, MD The Major T Cell Subsets p56 lck + T cells γ δ ε ζ ζ p56 lck CD8+ T cells γ δ ε ζ ζ Cα Cβ Vα Vβ CD3 CD8 Cα Cβ Vα Vβ CD3 MHC II peptide

More information

B and T cell Memory. Bengt Lindbom Adap6ve Immunity BMC D14

B and T cell Memory. Bengt Lindbom Adap6ve Immunity BMC D14 B and T cell Memory Bengt Lindbom Adap6ve Immunity BMC D14 Immunity: a historical perspec6ve 430 B.C. Thucydides describes the ongoing plague of Athens:.the same man was never attacked twice 15th century:

More information

Principles of Adaptive Immunity

Principles of Adaptive Immunity Principles of Adaptive Immunity Chapter 3 Parham Hans de Haard 17 th of May 2010 Agenda Recognition molecules of adaptive immune system Features adaptive immune system Immunoglobulins and T-cell receptors

More information

General Overview of Immunology. Kimberly S. Schluns, Ph.D. Associate Professor Department of Immunology UT MD Anderson Cancer Center

General Overview of Immunology. Kimberly S. Schluns, Ph.D. Associate Professor Department of Immunology UT MD Anderson Cancer Center General Overview of Immunology Kimberly S. Schluns, Ph.D. Associate Professor Department of Immunology UT MD Anderson Cancer Center Objectives Describe differences between innate and adaptive immune responses

More information

Supplementary Information:

Supplementary Information: Supplementary Information: Follicular regulatory T cells with Bcl6 expression suppress germinal center reactions by Yeonseok Chung, Shinya Tanaka, Fuliang Chu, Roza Nurieva, Gustavo J. Martinez, Seema

More information

Overview B cell development T cell development

Overview B cell development T cell development Topics Overview B cell development T cell development Lymphocyte development overview (Cont) Receptor diversity is produced by gene rearrangement and is random Includes specificities that will bind to

More information

Hematopoiesis. Hematopoiesis. Hematopoiesis

Hematopoiesis. Hematopoiesis. Hematopoiesis Chapter. Cells and Organs of the Immune System Hematopoiesis Hematopoiesis- formation and development of WBC and RBC bone marrow. Hematopoietic stem cell- give rise to any blood cells (constant number,

More information

PLAN. Réponses B thymodépendantes et thymoindépendantes. B cell development and classification. B cell activation. Thymodependent B(2) cell response

PLAN. Réponses B thymodépendantes et thymoindépendantes. B cell development and classification. B cell activation. Thymodependent B(2) cell response Réponses B thymodépendantes et thymoindépendantes PLAN B cell development and classification B cell activation Thymodependent B(2) cell response BMC 423 (IF) - 2007 Antonino Nicoletti Thymo-independent

More information

B cell differentiation: role of lympho-stromal interactions

B cell differentiation: role of lympho-stromal interactions cell differentiation: role of lympho-stromal interactions Claudine Schiff schiff@ciml.univ-mrs.fr http://www.ciml.univ-mrs.fr/lab/schiff.htm November 2009 Hematopoiesis Days of Gestation 8 11 12 Mutipotent

More information

Memory B cells. Tomohiro Kurosaki 1,2, Kohei Kometani 2,3 and Wataru Ise 1

Memory B cells. Tomohiro Kurosaki 1,2, Kohei Kometani 2,3 and Wataru Ise 1 Memory s Tomohiro Kurosaki 1,2, Kohei Kometani 2,3 and Wataru Ise 1 Abstract The immune system can remember a previously experienced pathogen and can evoke an enhanced response to reinfection that depends

More information

SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION Supplementary Text Results In vitro activation experiments established that treatment with anti-cd3 plus anti- CD28 was sufficient to promote EBI2 transcript on CD4 T cells (Extended Data Fig. 1d, e).

More information

The development of T cells in the thymus

The development of T cells in the thymus T cells rearrange their receptors in the thymus whereas B cells do so in the bone marrow. The development of T cells in the thymus The lobular/cellular organization of the thymus Immature cells are called

More information

Antigen Presentation and T Lymphocyte Activation. Abul K. Abbas UCSF. FOCiS

Antigen Presentation and T Lymphocyte Activation. Abul K. Abbas UCSF. FOCiS 1 Antigen Presentation and T Lymphocyte Activation Abul K. Abbas UCSF FOCiS 2 Lecture outline Dendritic cells and antigen presentation The role of the MHC T cell activation Costimulation, the B7:CD28 family

More information

Role of BAFF in B cell Biology and Autoimmunity

Role of BAFF in B cell Biology and Autoimmunity Role of BAFF in B cell Biology and Autoimmunity B cell development in health and disease: B-lymphocytes or B cells, and the antibodies they produce, are crucial mediators of humoral immunity, providing

More information

Chapter 11. B cell generation, Activation, and Differentiation. Pro-B cells. - B cells mature in the bone marrow.

Chapter 11. B cell generation, Activation, and Differentiation. Pro-B cells. - B cells mature in the bone marrow. Chapter B cell generation, Activation, and Differentiation - B cells mature in the bone marrow. - B cells proceed through a number of distinct maturational stages: ) Pro-B cell ) Pre-B cell ) Immature

More information

B Lymphocyte Development and Activation

B Lymphocyte Development and Activation Harvard-MIT Division of Health Sciences and Technology HST.176: Cellular and Molecular Immunology Course Director: Dr. Shiv Pillai 09/26/05; 9 AM Shiv Pillai B Lymphocyte Development and Activation Recommended

More information

Andrea s Final Exam Review PCB 3233 Spring Practice Final Exam

Andrea s Final Exam Review PCB 3233 Spring Practice Final Exam NOTE: Practice Final Exam Although I am posting the answer key for this practice exam, I want you to use this practice to gauge your knowledge, and try to figure out the right answer by yourself before

More information

Targeting the BLyS family in autoimmunity: a tale of mouse and man

Targeting the BLyS family in autoimmunity: a tale of mouse and man Therapeutic Perspective Targeting the BLyS family in autoimmunity: a tale of mouse and man Clin. Invest. (2011) 1(7), 951 967 Members of the B-lymphocyte stimulator (BLyS) family play key roles in B-lymphocyte

More information

Review Questions: Janeway s Immunobiology 8th Edition by Kenneth Murphy

Review Questions: Janeway s Immunobiology 8th Edition by Kenneth Murphy Review Questions: Janeway s Immunobiology 8th Edition by Kenneth Murphy Chapter 11 (pages 429-460): Dynamics of Adaptive Immunity prepared by Kelly von Elten, Walter Reed National Military Medical Center,

More information

Putting it Together. Stephen Canfield Secondary Lymphoid System. Tonsil Anterior Cervical LN s

Putting it Together. Stephen Canfield Secondary Lymphoid System. Tonsil Anterior Cervical LN s Putting it Together Stephen Canfield smc12@columbia.edu Secondary Lymphoid System Tonsil Anterior Cervical LN s Axillary LN s Mediastinal/Retroperitoneal LN s Thoracic Duct Appendix Spleen Inguinal LN

More information

Adaptive (acquired) immunity. Professor Peter Delves University College London

Adaptive (acquired) immunity. Professor Peter Delves University College London Adaptive (acquired) immunity Professor Peter Delves University College London p.delves@ucl.ac.uk Haematopoiesis Haematopoiesis Lymphocytes = adaptive response Recognition of pathogens by adaptive cells,

More information

CHARACTERISING HEPATIC B CELL SUBSETS IN HUMAN CHRONIC LIVER DISEASE

CHARACTERISING HEPATIC B CELL SUBSETS IN HUMAN CHRONIC LIVER DISEASE CHARACTERISING HEPATIC B CELL SUBSETS IN HUMAN CHRONIC LIVER DISEASE By Sudha Purswani BSc. (Hons.), MRes A thesis submitted to The University of Birmingham for the degree of DOCTOR OF PHILOSOPHY Centre

More information

research article Table 1 Features of XLP patients

research article Table 1 Features of XLP patients Research article Selective generation of functional somatically mutated IgM + CD27 +, but not Ig isotype switched, memory B cells in X-linked lymphoproliferative disease Cindy S. Ma, 1,2 Stefania Pittaluga,

More information

Regulation of Germinal Center Reactions by B and T Cells

Regulation of Germinal Center Reactions by B and T Cells Antibodies 2013, 2, 554-586; doi:10.3390/antib2040554 Review OPEN ACCESS antibodies ISSN 2073-4468 www.mdpi.com/journal/antibodies Regulation of Germinal Center Reactions by B and T Cells Young Uk Kim

More information

Characterization Of Human T-Bet-Expressing B Lymphocytes And Their Role In The Hiv Immune Response

Characterization Of Human T-Bet-Expressing B Lymphocytes And Their Role In The Hiv Immune Response University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2017 Characterization Of Human T-Bet-Expressing B Lymphocytes And Their Role In The Hiv Immune Response James Knox University

More information

Chapter 11. B cell generation, Activation, and Differentiation. Pro-B cells. - B cells mature in the bone marrow.

Chapter 11. B cell generation, Activation, and Differentiation. Pro-B cells. - B cells mature in the bone marrow. Chapter B cell generation, Activation, and Differentiation - B cells mature in the bone marrow. - B cells proceed through a number of distinct maturational stages: ) Pro-B cell ) Pre-B cell ) Immature

More information

7/6/2009. The study of the immune system and of diseases that occur as a result of inappropriate or inadequate actions of the immune system.

7/6/2009. The study of the immune system and of diseases that occur as a result of inappropriate or inadequate actions of the immune system. Diseases of Immunity 2009 CL Davis General Pathology Paul W. Snyder, DVM, PhD Purdue University Acknowledgements Pathologic Basis of Veterinary Disease, 4 th Ed Veterinary Immunology, An Introduction 8

More information

The Development of Lymphocytes: B Cell Development in the Bone Marrow & Peripheral Lymphoid Tissue Deborah A. Lebman, Ph.D.

The Development of Lymphocytes: B Cell Development in the Bone Marrow & Peripheral Lymphoid Tissue Deborah A. Lebman, Ph.D. The Development of Lymphocytes: B Cell Development in the Bone Marrow & Peripheral Lymphoid Tissue Deborah A. Lebman, Ph.D. OBJECTIVES 1. To understand how ordered Ig gene rearrangements lead to the development

More information

Immunological memory.

Immunological memory. Chapter 11: Dynamics of Adaptive Immunity the answers will lie in the cytokines produced by the environment and by the T cells themselves, and in the affinity of the T-cell receptors for their antigens.

More information

Practice Test. Test 5

Practice Test. Test 5 Practice Test Test 5 1) A plasma cell can directly differentiate from: a. An activated B cell. b. Isotype switched, somatically hypermutated centrocyte c. Memory B cell. d. A & B e. All of the above. 2)

More information

WHY IS THIS IMPORTANT?

WHY IS THIS IMPORTANT? CHAPTER 16 THE ADAPTIVE IMMUNE RESPONSE WHY IS THIS IMPORTANT? The adaptive immune system protects us from many infections The adaptive immune system has memory so we are not infected by the same pathogen

More information

1. Overview of Adaptive Immunity

1. Overview of Adaptive Immunity Chapter 17A: Adaptive Immunity Part I 1. Overview of Adaptive Immunity 2. T and B Cell Production 3. Antigens & Antigen Presentation 4. Helper T cells 1. Overview of Adaptive Immunity The Nature of Adaptive

More information

Chapter 3, Part A (Pages 37-45): Leukocyte Migration into Tissues

Chapter 3, Part A (Pages 37-45): Leukocyte Migration into Tissues Allergy and Immunology Review Corner: Chapter 3, Part A (pages 37-45) of Cellular and Molecular Immunology (Seventh Edition), by Abul K. Abbas, Andrew H. Lichtman and Shiv Pillai. Chapter 3, Part A (Pages

More information

5/1/13. The proportion of thymus that produces T cells decreases with age. The cellular organization of the thymus

5/1/13. The proportion of thymus that produces T cells decreases with age. The cellular organization of the thymus T cell precursors migrate from the bone marrow via the blood to the thymus to mature 1 2 The cellular organization of the thymus The proportion of thymus that produces T cells decreases with age 3 4 1

More information

Innate Signaling Pathways in the Maintenance of Serological Memory: A Dissertation

Innate Signaling Pathways in the Maintenance of Serological Memory: A Dissertation University of Massachusetts Medical School escholarship@umms GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2012-06-21 Innate Signaling Pathways in the Maintenance of Serological

More information

Immunology Basics Relevant to Cancer Immunotherapy: T Cell Activation, Costimulation, and Effector T Cells

Immunology Basics Relevant to Cancer Immunotherapy: T Cell Activation, Costimulation, and Effector T Cells Immunology Basics Relevant to Cancer Immunotherapy: T Cell Activation, Costimulation, and Effector T Cells Andrew H. Lichtman, M.D. Ph.D. Department of Pathology Brigham and Women s Hospital and Harvard

More information

Lymphoid System: cells of the immune system. Answer Sheet

Lymphoid System: cells of the immune system. Answer Sheet Lymphoid System: cells of the immune system Answer Sheet Q1 Which areas of the lymph node have most CD3 staining? A1 Most CD3 staining is present in the paracortex (T cell areas). This is towards the outside

More information

Vaccine Immunology HOW DO VACCINES MEDIATE PROTECTION? What Are the Main Effectors of Vaccine Responses? Claire-Anne Siegrist

Vaccine Immunology HOW DO VACCINES MEDIATE PROTECTION? What Are the Main Effectors of Vaccine Responses? Claire-Anne Siegrist Vaccine Immunology Claire-Anne Siegrist To generate vaccine-mediated protection is a complex challenge. Currently available vaccines have largely been developed empirically, with little or no understanding

More information

T cell-mediated immunity

T cell-mediated immunity T cell-mediated immunity Overview For microbes within phagosomes in phagocytes.cd4+ T lymphocytes (TH1) Activate phagocyte by cytokines studies on Listeria monocytogenes For microbes infecting and replicating

More information

Development of B and T lymphocytes

Development of B and T lymphocytes Development of B and T lymphocytes What will we discuss today? B-cell development T-cell development B- cell development overview Stem cell In periphery Pro-B cell Pre-B cell Immature B cell Mature B cell

More information

Ig light chain rearrangement: Rescue pathway

Ig light chain rearrangement: Rescue pathway B Cell Development Ig light chain rearrangement: Rescue pathway There is only a 1:3 chance of the join between the V and J region being in frame Vk Jk Ck Non-productive Rearrangement Light chain has a

More information

Antigen Presentation and T Lymphocyte Activation. Shiv Pillai MD, PhD Massachusetts General Hospital Harvard Medical School. FOCiS

Antigen Presentation and T Lymphocyte Activation. Shiv Pillai MD, PhD Massachusetts General Hospital Harvard Medical School. FOCiS 1 Antigen Presentation and T Lymphocyte Activation Shiv Pillai MD, PhD Massachusetts General Hospital Harvard Medical School FOCiS 2 Lecture outline Overview of T cell activation and the rules of adaptive

More information

Adaptive Immunity. Jeffrey K. Actor, Ph.D. MSB 2.214,

Adaptive Immunity. Jeffrey K. Actor, Ph.D. MSB 2.214, Adaptive Immunity Jeffrey K. Actor, Ph.D. MSB 2.214, 500-5344 Lecture Objectives: Understand role of various molecules including cytokines, chemokines, costimulatory and adhesion molecules in the development

More information

chapter 17: specific/adaptable defenses of the host: the immune response

chapter 17: specific/adaptable defenses of the host: the immune response chapter 17: specific/adaptable defenses of the host: the immune response defense against infection & illness body defenses innate/ non-specific adaptable/ specific epithelium, fever, inflammation, complement,

More information

Introduction to Immunology Part 2 September 30, Dan Stetson

Introduction to Immunology Part 2 September 30, Dan Stetson Introduction to Immunology Part 2 September 30, 2016 Dan Stetson stetson@uw.edu 441 Lecture #2 Slide 1 of 26 CLASS ANNOUNCEMENT PLEASE NO TREE NUTS IN CLASS!!! (Peanuts, walnuts, almonds, cashews, etc)

More information

Introduction to Immunology Lectures 1-3 by Bellur S. Prabhakar. March 13-14, 2007

Introduction to Immunology Lectures 1-3 by Bellur S. Prabhakar. March 13-14, 2007 Introduction to Immunology Lectures 1-3 by Bellur S. Prabhakar. March 13-14, 2007 TheComponents Of The Immune System and Innate Immunity: Ref: Immunobiology-5 th edition. Janeway et al. Chapters-1 & 2.

More information

Lecture 9: T-cell Mediated Immunity

Lecture 9: T-cell Mediated Immunity Lecture 9: T-cell Mediated Immunity Questions to Consider How do T cells know where to go? Questions to Consider How do T cells know where to go? How does antigen get targeted to a T cell expressing the

More information

CELL BIOLOGY - CLUTCH CH THE IMMUNE SYSTEM.

CELL BIOLOGY - CLUTCH CH THE IMMUNE SYSTEM. !! www.clutchprep.com CONCEPT: OVERVIEW OF HOST DEFENSES The human body contains three lines of against infectious agents (pathogens) 1. Mechanical and chemical boundaries (part of the innate immune system)

More information

B cell development in the bone marrow.

B cell development in the bone marrow. development in the bone. s develop from multipotent haematopoietic stem s in the bone that produce lymphoid progenitors which in turn generate s. s with a unique antibody specificity develop by initial

More information

CD4+ T Helper T Cells, and their Cytokines in Immune Defense and Disease

CD4+ T Helper T Cells, and their Cytokines in Immune Defense and Disease CD4+ T Helper T Cells, and their Cytokines in Immune Defense and Disease Andrew Lichtman M.D., Ph.D. Brigham and Women s Hospital Harvard Medical School Lecture outline Intro to T cell mediated immunity

More information

Molecular Pathology of Lymphoma (Part 1) Rex K.H. Au-Yeung Department of Pathology, HKU

Molecular Pathology of Lymphoma (Part 1) Rex K.H. Au-Yeung Department of Pathology, HKU Molecular Pathology of Lymphoma (Part 1) Rex K.H. Au-Yeung Department of Pathology, HKU Lecture outline Time 10:00 11:00 11:15 12:10 12:20 13:15 Content Introduction to lymphoma Review of lymphocyte biology

More information

The T cell receptor for MHC-associated peptide antigens

The T cell receptor for MHC-associated peptide antigens 1 The T cell receptor for MHC-associated peptide antigens T lymphocytes have a dual specificity: they recognize polymporphic residues of self MHC molecules, and they also recognize residues of peptide

More information

The Adaptive Immune Responses

The Adaptive Immune Responses The Adaptive Immune Responses The two arms of the immune responses are; 1) the cell mediated, and 2) the humoral responses. In this chapter we will discuss the two responses in detail and we will start

More information

Chapter 1. Chapter 1 Concepts. MCMP422 Immunology and Biologics Immunology is important personally and professionally!

Chapter 1. Chapter 1 Concepts. MCMP422 Immunology and Biologics Immunology is important personally and professionally! MCMP422 Immunology and Biologics Immunology is important personally and professionally! Learn the language - use the glossary and index RNR - Reading, Note taking, Reviewing All materials in Chapters 1-3

More information

SOPHOMORE DENTAL/OPTOMETRY MICROBIOLOGY SECTION: IMMUNOLOGY CELLS AND ORGANS OF THE IMMUNE SYSTEM

SOPHOMORE DENTAL/OPTOMETRY MICROBIOLOGY SECTION: IMMUNOLOGY CELLS AND ORGANS OF THE IMMUNE SYSTEM SOPHOMORE DENTAL/OPTOMETRY MICROBIOLOGY SECTION: IMMUNOLOGY CELLS AND ORGANS OF THE IMMUNE SYSTEM Lecturer: Dr. John F Kearney 934-6557 jfk@uab.edu Objectives: To learn: 1) the basic cell types that make

More information

Effector mechanisms of cell-mediated immunity: Properties of effector, memory and regulatory T cells

Effector mechanisms of cell-mediated immunity: Properties of effector, memory and regulatory T cells ICI Basic Immunology course Effector mechanisms of cell-mediated immunity: Properties of effector, memory and regulatory T cells Abul K. Abbas, MD UCSF Stages in the development of T cell responses: induction

More information

Hematopoiesis. BHS Liège 27/1/2012. Dr Sonet Anne UCL Mont-Godinne

Hematopoiesis. BHS Liège 27/1/2012. Dr Sonet Anne UCL Mont-Godinne Hematopoiesis BHS Liège 27/1/2012 Dr Sonet Anne UCL Mont-Godinne Hematopoiesis: definition = all the phenomenons to produce blood cells Leukocytes = White Blood Cells Polynuclear = Granulocytes Platelet

More information

REGULATION OF THE GERMINAL CENTER REACTION BY T HELPER CELLS AND T REGULATORY CELLS

REGULATION OF THE GERMINAL CENTER REACTION BY T HELPER CELLS AND T REGULATORY CELLS REGULATION OF THE GERMINAL CENTER REACTION BY T HELPER CELLS AND T REGULATORY CELLS Hao Wu Submitted to the faculty of the University Graduate School in partial fulfillment of the requirements for the

More information

Micro 204. Cytotoxic T Lymphocytes (CTL) Lewis Lanier

Micro 204. Cytotoxic T Lymphocytes (CTL) Lewis Lanier Micro 204 Cytotoxic T Lymphocytes (CTL) Lewis Lanier Lewis.Lanier@ucsf.edu CTL Recognition of antigen Generation. priming via dendritic cells Effector functions..killing and cytokines Cytolytic process

More information

IMMUNE CELLS AND TYPE I INTERFERON IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENT URINE AND KIDNEY IMMUNOPATHOLOGY

IMMUNE CELLS AND TYPE I INTERFERON IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENT URINE AND KIDNEY IMMUNOPATHOLOGY IMMUNE CELLS AND TYPE I INTERFERON IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENT URINE AND KIDNEY IMMUNOPATHOLOGY Eric Scott A dissertation submitted to the faculty at the University of North Carolina at Chapel

More information

IgG3 Complements IgM in the Complement-Mediated Regulation of Immune Responses

IgG3 Complements IgM in the Complement-Mediated Regulation of Immune Responses Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1310 IgG3 Complements IgM in the Complement-Mediated Regulation of Immune Responses LU ZHANG ACTA UNIVERSITATIS UPSALIENSIS

More information