Regulation of the IgE Antibody Response

Regulation of the IgE Antibody Response

Progress in Allergy vaι. s2 Series Editors Kimishige Ishizaka, Baltimore, Md.; Paul KaΙΙόs, Helsingborg; Byron H. Waksman, New York, N.Y., and Alain L. de Weck, Bern S. Karger Basel München Paris London New York Sydney

Regulation of the IgE Antibody Response Volume Editor Kimishige Ishizaka, Baltimore, Md. Contributors H. Bazin, Brussels; K. Blaser, Bern; B.E. Bozelka, New Orleans, La.; K. Ishizaka, Baltimore, Md.; D.H. Katz, La Jolla, Calif.; T. Kishimoto, Osaka; S.B. Lehrer, New Orleans, La.; P.S. Norman, Baltimore, Md.; R. Pauwels, Ghent; A.H. Sehon, Winnipeg, Manit.; A.L. de Weck, Bern 68 figures and 51 tables, 1982 S. Karger Basel München Paris London New York Sydney

Progress in Allergy Vol. 29: Ontogeny of the Immune System. B.H. Waksman, New York, N.Y. (ed.) XII + 268 p., 10 fig., 18 tab., 1981. ISBN 3-8055-2434-X Vol. 30: Recent Trends in Allergen and Complement Research. P. Ka11ós, Helsingborg (ed.) XIV+234 p., 56 fig., 32 tab., 1982. ISBN 3-8055-2580-X Vol. 31: Immunity and Concomitant Immunity in Infectious Diseases. P. Kallόs, Helsingborg (ed.) ISBN 3-8055-3464-7 National Library of Medicine, Cataloging in Publication Regulation of the 'ge antibody response Volume editor, Kimishige Ishízcrka; contributors, H. Bazin (et al.], - Basel, New York, Karger 1982 (Progress in Allergy; v. 32) 1.IgE-immunology I. Ishizaka, Kimishige Π. Series W1 PR666F v. 32/QW 601 R344 ISBN 3-8055-3470-1 Drug Dosage The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flew of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. All rights reserved No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Copyright 1982 by S. Karger AG, P.O. Box, CH-4009 Basel (Switzerland) Printed in Switzerland by Buchdruckerei `Der Bund' Bern ISBN 3-8055-3470-1

Contents Introduction K. Ishizaka, Baltimore, Md 1 Mouse IgE S.B. Lehrer; B.E. Bozelka, New Orleans, La. 8 Introduction 9 Why Mouse IgE? 9 Historical Background 10 IgE Biosynthesis 11 Cellular Interactions 11 Site of Synthesis 12 Stimulation of IgE Production 13 Antigen 13 Adjuvants 13 Parasite Infection 14 Non-Specific Methods 14 Suppression of Reaginic Antibody Production 15 Suppressor Cells 15 Tolerance 16 Idiotype Suppression 17 Isotype Suppression 17 Other Mechanisms 20 Ontogeny 20 IgE Isolation 21 IgE from Serum and Ascites Fluid 21 Source of IgE 21 Detection of IgE 23

Contents ΝΙ Purification of 1gB 24 IgB Hybridomas 30 IgB Properties 33 Physicochemical Properties 33 Immunochemical Properties 34 Biological Properties 35 Biological Significance of IgB 36 Allergic Reactions 36 Parasite Infection 37 Neoplasia 37 Future Direction 38 Acknowledgements 39 References 39 IgE and Ig2a Isotypes in the Rat H. Bazin; R. Pauwels, Brussels/Ghent 52 Historical Background 53 Rat Plasmacytoma Tumours 53 Introduction 53 Origin of the LOU Strain 55 Ileocaecal Malignant Immunocytomas 56 Biosynthesis of Rat Monoclonal Immunoglobulins 59 Production of 1gB Monoclonal Immunglobulins 59 Purification of Normal or Monoclonal IgB 61 Hybridomes 63 Antiserum to Rat IgB 63 Purification of Normal or Monoclonal IgG2a 64 Antiserum to Rat IgG2a 64 Physico-Chemical Properties of Rat IgB 64 Physico-Chemical Properties of Rat IgG2a 66 Biological Properties of Rat 1gB 67 Measurement of IgB 68 Biological Properties of Rat IgG2a 71 Measurement of IgG2a 72 Regulation of IgB Production 73 Ontogeny 73 Soluble Factors Implicated in the IgB Production 79 Localization of Rat IgB Cells 82 Effect of Antigen on IgB Synthesis 83 Effect of Adjuvant on the IgB Antibody Response in the Rat 86 Effect of Age on the IgB Antibody Response in Rats 88 Genetic Control of the IgB Immune Response 89 Regulation of IgG2a Production 93 References 94

Contents VΙΙ IgE Antibody Responses in vitro: from Rodents to Man D.H. Katz, La Jolla, Calif. 105 Introduction 105 Variations in Systems Employed for in vitro IgE Synthesis 106 Synthesis of IgE by Cultured Rabbit Lymphoid Cells 107 In vitro Stimulation of Rat Lymphoid Cells To Become IgE-Producing Cells 108 Ιn vitro Biosynthesis of IgE by Cultured Mouse Lymphoid Cells 110 In vitro Biosynthesis of IgE by Human Peripheral Blood Mononuclear Cells 114 Culture Systems in which PWM Failed To Stimulate IgE Synthesis 115 Culture Systems in which PWM Stimulated IgE Synthesis 118 Explanations for the Conflicting Findings on the Ability of PWM To Stimulate Human IgE Synthesis in vitro 125 Stimulation of Human IgE Synthesis in vitro by Soluble Antigen or a Mixture of Soluble Antigen plus PWM 126 Lymphocytes Expressing Specific Fc Receptors for IgE (FcRε) 130 Soluble Factors Regulating IgE Responses in vitro 136 IgE B Cell Generating Factor Derived from Rat Lymphoid Cells 137 Regulatory Factors with Binding Amnity for IgE 139 Serum-Derived Suppressive Factor of Allergy and Enhancing Factor of Allergy 144 Conclusions 151 Acknowledgments 152 References 152 Suppression of IgE Antibody Responses with Tolerogenic Conjugates of Allergens and Hoptens Α.H. Sehon, Winnipeg, Manít. 161 Introduction 161 Current Hyposensitization Methods for IgE-Mediated Allergies 162 Brief Overview of Cellular Interactions Regulating the Antibody Response with Reference to IgE Production 165 New Strategies for the Specific Downregulation of the IgE Response 168 Use of Immunosuppressive Conjugates of Isologous y-globulins or of Copolymers of D-Glutamic Acid and D-Lysine with Hoptens and Proteins 169 Generation of Suppressor T Cells by Modified Allergens 170 Antigen-PEG Systems 171 Hapten-PIA Systems 180 Relationship between Suppression of Circulating IgE Antibodies and the State of Sensitivity of Animals Treated by Tolerogenic Conjugates 187 Suppression of Systemic Sensitivity of RAG-Sensitive Dogs Following Treatment with RAG-mPEG Conjugates 187 Suppression of Systemic Sensitivity of BPO-Sensitive Mice Following Treatment with BPO-PVA Conjugates 189

Contents VIII Conclusions 193 Acknowledgements 194 References 194 Regulation of the IgE Antibody Response by Idiotype-Anti-Idiotype Network K. Blaser; A.L. de Weck, Bern 203 Idiotype-Anti-Idiotype Regulation: Current State 204 Introduction 204 Regulation of the Immune Response by a Network of Idiotypes 206 Complementary Idiotypes as Receptors on B Lymphocytes 207 Complementary Idiotypes as Receptors on Subsets of T Lymphocytes 207 A Possible Regulatory Pathway for T-Dependent Anti-Hapten Responses 212 Manipulations of the Immune Response by Interaction with the Regulatory Circuit of Complementary Idiotypes 213 Regulation of IgE Antibody Formation by the Idiotype-Anti-Idiotype Network 220 Introduction 220 Phosphorylcholine System 221 Benzylpenicilloyl System 222 L-Glutamic Acid60-L-Alanineó0-L-Tyrosine10 System 223 Azobenzenearsonate System 223 4-Hydroxy-3-Nitrophenyl-Acetly System 223 Regulatory Effects of Actively Induced Anti-Idiotypes on the Formation of IgE Antibodies 224 Production and Characterization of Anti-Hapten and Anti-Idiotypic Antibodies 224 Regulatory Effects of Anti-Idiotypes in Mice Actively Immunized with Syngeneic Antibodies 226 Regulatory Effects of Anti-Idiotypes in Guinea Pigs Actively Immunized with Syngeneic Antibodies 236 In Man 238 Effects of Passively Administered Anti-Idiotypic Antibodies 238 In BALB/c Mice 238 In Guinea Pigs 242 In Man 243 Suppression of Antibody Response by Anti-Hapten- and Anti-Carrier Anti- Idiotypic Antibodies. Anaphylactogenic Properties of Anti-Idiotypic Antibodies 243 Effects of Antigen Coupled to Syngeneic Spleen Cells 245 Peculiarities of IgE Regulation in Respect to Regulation of Other Antibody Classes and of Cell-Mediated Immunity 247 Perspectives for the Future 249 References 251

Contents IX IgE Class-Specific Suppressor T Cells and Regulation of the IgE Response T. Kishimoto, Osaka 265 Introduction 265 Cells Involved in the IgE Antibody Response 266 Interaction of T and B Cells in the IgE Response 266 IgE Class-Specific Helper T Cells and Isotype-Specific Regulation of the Antibody Response 268 Induction and Characterization of IgE Class-Specific Suppressor T Cells 271 Induction of ΙgE Class-Specific Suppressor T Cells 271 Are ΙgE Class-Specific Suppressor T Cells Antigen-Specific or Non-Specific? 274 Suppression of the in vivo IgE Response by Suppressor T Cells 278 T Cell Factors Regulating the ΙgE Antibody Response 283 ΙgE Class-Specific Helper or Potentiating Factor(s) 283 IgE Class-Specific Suppressor Factor(s) 286 Target Cells of ΙgE Class-Specific Suppressor Factor(s) 291 ΙgE Class-Specific Suppressor T Hybridoma and Its Products 299 IgE-B Cells, the Target Cells of IgE Class-Specific Suppressor Factor 303 Conclusion and Future Prospects 307 Acknowledgment 310 References 310 Immunotherapy P.S. Norman, Baltimore, Md. 318 Introduction 318 `Prophylactic Inoculations' 319 Desensitization 320 Blocking Antibodies 320 Controlled Studies 321 Immunologic Correlates 323 ΙgE Antibodies 326 Specificity of Immunotherapy 327 Antibodies in Secretions 329 Clinically Useful Allergens for Immunotherapy 331 Problem Areas 333 Depot Methods 334 Cross-Linked or Polymerized Antigens 335 Lymphocyte Reactions 336 Suppression of IgE Antibodies 337 References 339