Differentiation of B Lymphocytes PDF
Preview Differentiation of B Lymphocytes
Current Topics in Microbiology 135 and Immunology Editors A. Clarke, Parkville/Victoria . R W. Compans, Birmingham/Alabama . M Cooper, Birmingham/Alabama H. Eisen, Paris . W. Goebel, Wilrzburg . H. Koprowski, Philadelphia . F. Melchers, Basel . M Oldstone, La Jolla/California· P.K Vogt, Los Angeles H. Wagner, U1m . I. Wilson, La Jolla/California Differentiation of B Lymphocytes Edited by C.J. Paige and RH. Gisler With 25 Figures Springer-Verlag Berlin Heidelberg NewY ork London Paris Tokyo Dr. CHRISTOPHER J. PAIGE Dr. ROLAND H. GISLER Basel Institute for Immunology Grenzacherstrasse 487 CH-4058 Basel ISBN-13: 978-3-642-71853-3 e-ISBN-13: 978-3-642-71851-9 DOl: 10.107/978-3-642-71851-9 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks. Under § 54 of the German Copyright Law where copies are made for other than private use, a fee is payable to "Verwertungsgesellschaft Wort", Munich. © Springer-Verlag Berlin Heidelberg 1987 Softcover reprint of the hardcover 1st edition 1987 Library of Congress Catalog Card Number 15-12910 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product Liability: The publisher can give no guarantee for information about drug dosage and application thereof contained on this book. In every individual case the respective user must check its accuracy by consulting other pharmaceuti cal literature. 2123/3130-543210 Preface Rapid progress continues to be made in understanding the molecular and cellular events that comprise B-Iymphocyte differentiation. This is due in part to the high level of inter est shown by many investigators from diverse disciplines, who find this subject suitable for addressing some of the fundamental issues of immunobiology. B-cell developmen tal models are being extensively used to investigate cell-cell interactions, molecular mediators of differentiation and proliferation, differential onset of gene programs, and gene rearrangement and expression, as well as the generation of the immune response itself. Not surprisingly, increased understanding of B-cell differentiation sometimes results from the application of new techniques that permit greater insight into the cells comprising the system and the genetic mechanisms by which these cells express their differentiative potential. However, experimental strategies based upon the novel application of established technologies have also led to the clarification of many issues, as well as to the discov ery of previously unrecognized problems. One problem, well recognized by those active in the field, is how to keep up with significant developments as they appear. The purpose of this book, part of a series devoted to analysing current issues in biology, is to help overcome this problem. No attempt at comprehensive cov erage of all of the issues has been made. Rather, a more thorough analysis of a few topics is presented. The first section deals with cellular models of differentiation and covers attempts, both in vivo and in vitro, to understand B-cell development. As it has become increasingly apparent that different species may well use different strategies to achieve the requisite degree of antibody diversity needed for the generation of an adequate repertoire, we have in cluded chapters which present the avian and ovine systems in contrast to the standard murine models. The second sec tion deals with molecular analyses of immunoglobulin gene formation, with particular emphasis on variable-region gene utilization. Also discussed are the immunoglobulin VI Preface class switch during B-cell differentiation and attempts to define genes expressed uniquely during B-cell development. We thank Leslie Nicklin of the Basel Institute for Im munology for editorial assistance in the preparation of this volume. Basel,1987 CHRISTOPHER J. PAIGE ROLAND H. GISLER Table of Contents P.W. KINCADE, P.L. WITTE, and K.S. LANDRETH: Stromal Cell and Factor-Dependent B Lymphopoiesis in Culture. With 4 Figures . 1 K. DORSHKIND and O.N. WITTE: Long-Term Murine Hemopoietic Cultures as Model Systems for Analysis of B-Lymphocyte Differentiation. With 5 Figures . . . . . . . . . . . . . .. . 23 J.D. REYNOLDS: Peyer's Patches and the Early Development of B Lymphocytes. With 3 Figures 43 J.R.L. PINK and O. LASSILA: B-Cell Commitment and Diversification in the Bursa of Fabricius. With 1 Figure .................. 57 H. SAUTER and C.J. PAIGE: Differentiation of Murine B-Cell Progenitors in Agar Culture: Determination of the Developmental Potential of Clonable Pre-B Cells ... . . . . . . . . . . . . 65 B.A. MALYNN, J.E. BERMAN, G.D. YANCOPOULOS, C.A. BONA, and F.W. ALT: Expression of the Immunoglobulin Heavy-Chain Variable Gene Repertoire ............... 75 R.M. PERLMUTTER: Programmed Development of the Antibody Repertoire. With 2 Figures . . . .. 95 J.-C. WEILL, M. LEIBOWITCH, and C.-A. REYNAUD: Questioning the Role of the Embryonic Bursa in the Molecular Differentiation of B Lymphocytes. With 8 Figures .............. 111 P.D. BURROWS and H. KUBAGAWA: Immunoglobulin Gene Rearrangements in Pre-B Cells. With 1 Figure .................,. 125 VIII Table of Contents N. SAKAGUCHI, C.N. BERGER, and F. MELCHERS: Cloning of Murine B-Lymphocyte Differentiation Stage-Specific Genes. With 1 Figure 139 Subject Index 149 Indexed in Current Contents List of Contributors You will find the addresses at the beginning of the respective contribution ALT, F.W. 75 MELCHERS, F. 139 BERGER, C.N. 139 PAIGE, C.J. 65 BERMAN, J.E. 75 PERLMUTTER, R.M. 95 BONA, C.A. 75 PINK, J .R.L. 57 BURROWS, P.D. 125 REYNAUD, C.-A. 111 DORSHKIND, K. 23 REYNOLDS, J.D. 43 KINCADE, P.W. 1 SAKAGUCHI, N. 139 KUBAGAWA, H. 125 SAUTER, H. 65 LANDRETH, K.S. 1 WEILL, J.-c. 111 LASSILA, O. 57 WITTE,O.N. 23 LEffiOWITCH, M. 111 WITTE, P.L. 1 MALYNN, B.A. 75 YANCOPOULOS, G.D. 75 Stromal Cell and Factor-Dependent B Lymphopoiesis in Culture P.W. KINCADE, P.L. WITTE, and K.S. LANDRETH 1 Introduction 1 2 A Theoretical Model for B-Lymphocyte Formation 3 General Approaches Involving Lymphoid Cell Cultures 4 4 Long-Term Bone Marrow Cultures 5 5 Interculture Variability and the Nature of Cultured Lymphocytes 5 6 Nonlymphoid Adherent Cells 10 7 Cells with Potential for Growth in Long-Term Lymphocyte Cultures 11 8 A Cloned Tumor Cell Model 12 9 Soluble Factors Influencing B-Cell Precursors 14 10 Synthesis and Concluding Remarks 16 References 17 1 Introduction Only a fraction of the cells responsible for humoral immunity (B lymphocytes) are long lived. While some B cells are made by division of other B lymphocytes during the propagation of immune responses, large numbers are continuously produced from immature precursors within hemopoietic tissues such as bone marrow. Recent technological advances have allowed substantial progress to be made in understanding the processes involved in primary B-cell formation and how they are regulated. This is particularly true for the final events in the series because they can be observed in cell culture. On the other hand, findings made with cell cultures provide exceptions to current hypotheses and it is now appropriate to reevaluate those models. Our objectives here are to present recent unpublished findings from in vitro studies, relate these to a general model which has been derived largely from transplantation and whole-animal work, and highlight new avenues of investigation which seem to hold particular promise. 2 A Theoretical Model for B-Lymphocyte Formation Panels of monoclonal antibodies can be used to identify committed progenitors ofB cells, manipulate them experimentally, and construct a probable differentia- Oklahoma Medical Research Foundation, 825 NE, 13th Street, Oklahoma City, OK 73104, USA Current Topics in Microbiology and Immunology, Vol. 135 © Springer-Verlag Berlin' Heidelberg 1987 2 P.W. Kincade et al. Large Small Newly Hemopoietic ? B Lineage Pre-B Pre-B Formed Stem Cell Precursor Cell Cell B Cell Fig. 1. Possible relationships between precursors of murine B lymphocytes. The model emphasizes the normal expression of an antigen on lymphocytes in adult bone marrow. Normal and leukemic cells in culture provide exceptions to this apparent sequence of events, as detailed in the text tion sequence for the final steps in de novo lymphopoiesis (KINCADE 1981; KINCADE and PHILLIPS 1985; Fig. 1). Our model was constructed from several experimental findings. All of the precursor cells in adult murine bone marrow which could quickly become functional B cells in culture, and 70% of those which did so in 10-day transfer experiments, could be depleted with our mono clonal 14.8 antibody (KINCADE et al. 1981 b; LANDRETH et al. 1983). Most of the lymphocytes in marrow could be highly enriched with this antibody and the suspensions included large and small cells. Approximately one-half of the selected 14.8-bearing (14.8+) lymphocytes which lacked surface immunoglobulin contained the ~ heavy chains of IgM. These "pre-B" cells had earlier been postulated to be the immediate precursors of B cells (RAFF et al. 1976; COOPER 1981). Other studies suggested that large pre-B cells normally divided just once before giving rise to small pre-B cells, which then matured without further divi sion by acquiring surface IgM (LANDRETH et al. 1981). Large cells sorted with a similar monoclonal antibody had extensively rearranged heavy-chain immuno globulin genes, whereas only the small cells had undergone light-chain gene rearrangement (COFFMAN and WEISSMAN 1983). Not shown in our diagram is the order of acquisition of various other surface markers (Lyb-2, Fc receptors, Th-B, la, etc.) which characterize mature, functional B lymphocytes in mice. Variations in assay techniques and the use of different inbred mouse strains make it difficult to integrate the available information in this way. While such theoretical models have been, and continue to be, most useful for experimental design, some caution is advised about their literal use, especially in interpreting culture results. We have stressed that the initial emergence of B-Iymphocyte lineage cells in ontogeny might differ substantially from the pro cess which occurs in adult marrow and have cited examples where initial surface antigen expression was dependent on chronological age, rather than on position in a differentiation sequence (KINCADE 1981, 1984; KINCADE et al. 1982). It was found that most pre-B cells in early embryos lack detectable 14.8 (VELARDI and COOPER, 1984; MEDLOCK et al. 1984), whereas the model indicates that cytoplasmic ~-chains would only be seen in 14.8 + lymphocytes. After approxi mately 16 days of gestation, all pre-B cells are 14.8+ and, while the marker is expressed on a subpopulation of peripheral T cells, there is no evidence that it is associated with myeloid cells (KINCADE et al. 1981 b; LANDRETH et al. 1983; SCHEID et al. 1982).
The list of books you might like
