Immunoglobulin genes

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The power of genetics Mechanisms of Segmentation; D e v e l o p m e n t , Vol. 104, Supplement edited by V. French, P. Ingham, J. Cooke and J. Smith, The Company

of Biologists, 1988. £40.00/$75.00 (250pages) ISBN O948601 15 9 One of the central questions of developmental biology is the mechanism responsible for establishing the overall body plan of the adult. Many organisms, notably annelids and arthropods, are composed of obvious compartments or segments. Following the establishment of these compartments, each compartment then differentiates in a unique way to produce the structures which give that segment its unique characteristics. Recent progress toward an understanding of the genetic basis of segmentation in Drosophila has made the study of segmentation an exciting and fast moving area of developmental biology. The Mechanisms of Segmentation is a special volume of Development which provides an overview of much of this progress. This volume consists of papers presented at a meeting of the British Society for Developmental Biology held in April 1988 at the University of Bristol. Over half of the papers in the volume are devoted to the progress which has been made in Drosophila. A variety of different gene classes have been shown to have roles in the establishment and differentiation of segments in Drosophila. The first are called maternal effect genes, which divide the egg into three d o m a i n s - anterior, posterior and terminal. The evidence to date, as presented or reviewed in several of these papers is consistent with the notion that morphogen gradients are established as a consequence of the activity of these genes. Once this asymmetry has been established, fertilization leads to activation of three different types of zygotic segmentation genes. (1) Segment polarity genes whose activity is required in every segment. Mutations in these genes remove a part of each segment. (2) Pair-rule genes which are expressed with a two segment periodicity. Pair-rule mutants therefore lack alternate structures. (3) Gap genes are expressed in contiguous segments. Consequently, gap gene mutants have 'gaps' in their segmental organization, missing one or more segments. These zygotic genes act and interact, appar-

ently to regulate expression of the genes which lead to production of the structures responsible for the specific characteristics of a given segment. Nearly everyone who reads scientific journals has seen the in situ hybridizations and immuno-localization studies which have contributed greatly to current ideas about the function and interactions between these genes. Particularly relevant to the interactions between these genes are the widely publicized results demonstrating that several of the zygotic genes encode proteins which are likely to bind specific D N A sequences. The experimental data consists of localization of gene products, and correlation of the presence or absence of these proteins with the phenotype observed. The papers in this collection suggest that much current effort is directed toward determining the effects of pairwise double mutants such as a pair-rule zygotic gene mutation in the presence of a maternal effect mutation. Soon we can expect to see a giant matrix which catalogs these interactions. For those of us who are not Drosophila geneticists, the papers in this collection provide a clear sense of what is known, as well as what needs to be learned. It is also a testament to both the power of genetics and the complexity of the segmentation process. We have learned an enormous amount from the elegant genetic and developmental studies of Drosophila segmentation. Several of the authors point out that the analysis of other sys-

tems, using what we have learned from Drosophila is likely to teach us even more. Several systems where this work has begun are described, including leech, crustaceans and mice. More traditional types of experiments, involving the use of brief periods of exposure to heat shock, or mitotic inhibitors to disrupt normal pattern formation in zebrafish, frogs and mice lead to the suggestion that processes similar to those observed in Drosophila may occur during development of higher organisms. The application of Drosophiladerived gene probes may provide an important first step in several organisms which are not as amenable to study as Drosophila, but which have important lessons to teach us. The striking localization of homeo-gene transcripts to somites in mouse embryos suggests that this approach will be rewarding. Because the homeobox containing genes seem likely to be DNA-binding proteins, it is certainly enticing to think of them as regulatory genes. Eventually it will be interesting to pursue the identification of the genes which they may regulate. In summary, this collection of articles provides a snapshot of the state of knowledge of segmentation as of April 1988. Of course, it seems the mail is bringing updates on a nearly weekly basis. This need not detract from the value of this collection. It will serve as a useful starting point for anyone interested in learning about how segmentation might work. R E X L. C H I S H O L M

Cell Biology and Anatomy, Northwestern University, Chicago, IL 60611, USA.

One hundred years of antibodies Immunoglobulin Genes edited by F. W. Alt, T. Honjo and T. H. Rabbitts, Academic Press, 1989.

£40.00 (xiii+410 pages) ISBN 0 12 354865 9 An enormous amount of information has been accumulated about the immunoglobulin molecule since its identification as a constituent of the serum almost 100 years ago. Many of the problems formulated during the last century have been answered with the advent of recombinant D N A technology during the last decade or so. To compile a volume reviewing our present understanding of immunoglobulin

genes is a formidable task and the editors and contributing authors of the book, all highly respected within the field, are to be congratulated on providing such a variety of informative and interesting articles. The strength of the book resides, like the immune system itself, in its diversity. There are 19 chapters which cover the main areas of current research. The first section introduces the reader to the fundamental aspects of B-cell development in both mammals and birds and includes a discussion of the problems associated with the maintenance of B lymphocytes in culture. The more inexperienced reader may find the second chapter on the development and growth

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control of B lymphocytes too complicated, the chapter containin~g too much of the jargon for which immunology is infamous. Readers should ne,vertheless persevere, to enjoy the more readable sections of the book. On the more positive side, the inclusion of ch~Lptersconcerned with the cellular aspects of immunoglobulin serves to remind us that the immune system is a complicated cellular network and not simFly a collection of rearranging genetic loci. The rearranging loci are described in great detail. Included along with those detailing the more familiar mammalian gene organization and rearrangement are excellent chapters describing the development of the antibody repertoire in the chicken and the organization of immunoglobulin genes in lower vertebrates. Although these species share certain features of the mammalian system, they display important differences in the organization of gene segments and the subsequent generation of antibody diversity and their inclusion allows the reader to compare the processes directly. It is now recognized thzLtthe basic structural unit of the immurLoglobulin molecule, the immunoglobulin fold, is a structural component of a number of other proteins including the T-cell antigen receptor molecules as well as a large number of molecules whose genes do not rearrange. The conservation of this structure is believed to reflect a functional similarity between these molecules; that of molecular recognition. Both the structural and evolutionary aspects of the immunoglobulin superfamily are discussed. As our understanding of the regulation of immunoglobulin gene expression grows, it is likely that research into certain disorders of the immune system will increase considerably. Immunoglobulin in disease is discussed within the context of immunoglobulin deficiencies, autoimmunity and neoplasia. This section provides a concise introduction to the area and focuses on the general principles underlying these events. This gives the reader the opportunity to grasp the basic information which is so often lacking in tile lengthier, more specialist articles. As well as being important from a clinical perspective, many disorders can provide clues as to the regulation of immunoglobulin gene expression in a normal environment. For instance, whilst it is clear that certain immunoglobulin deficiencies result from genetic lesions within the immunoglobulin loci themselves, a number of defects m~p outside

the locus. Lesions lying outside the locus presumably affect genes encoding proteins important in lymphocyte development or antibody expression itself. Studies on the expression of immunoglobulin, at both the molecular and cellular levels, have been aided by the use of transgenic mice. The types of experiments carried out and the major conclusions drawn from such studies are introduced. Transgenic mice are not a subject themselves but an experimental technique, and this chapter contains information on how this technique has contributed to the tackling of problems alluded to elsewhere in the volume. Studies on immunoglobulin gene expression have focused not only on the immunological aspects of regulation but also on those of more widespread interest such as differential RNA splicing and tissue-specific transcription. Both of these subjects are described in some detail. It is unfortunate but inevitable that a review of fast moving and popular topics will suffer from the delay that is inherent in publishing a volume of this size and this is revealed, for example, in the chapter concerning transcription factors. However, this chapter provides a useful introduction to this rapidly progressing field and the basic underlying mechanisms are established, notably the

existence of lymphoid specific DNA binding proteins which interact with heavy and light chain promoters and enhancers. Another area that has undergone rapid progress has been the construction and expression of chimaeric antibodies. At first sight this chapter appears somewhat out of place alongside the more fundamental aspects of immunoglobulin genes, however those readers who are new to the field will hopefully realize how the mountain of information on immunoglobulin genes can be translated into practical use. Overall, this volume is well written and well presented. This book will be of great use to those just beginning a career in immunology or to those in other fields wishing to familiarize themselves with the subject. Our main reason for agreeing to review the book was that we would learn something beyond mammalian antibody gene expression, which we certainly did. Those within the field of immunology would benefit from its overview and will no doubt find further interesting problems posed by the 100 years of research. S. PETrERSSON G. COOK

MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.

Molecular sensuality Design of E n z y m e Inhibitors as Drugs edited by Merton Sandier and H. John Smith, Oxford University Press, 1989. £90.00 (v + 810 pages) ISBN 0 19 261537 8 The design of molecules that selectively seek metabolic targets or receptors to secure control for the betterment of the host is an elusive aim that currently occupies vast industrial resources and the intellectual time of large numbers of research teams and individuals throughout the world. Professor Merton Sandier and Dr H. J. Smith should be complimented in having assembled a series of reviews from some of the more notable figures at the forefront in this research. It is important that an attempt has been made to cover so many areas, as the complexity of each area can allow the individual absorbed in only one to lose sight of the overall picture. This book is also timely in so

far as the field is at a fascinating transition point. The knowledge of biochemistry or molecular biology is, in many cases, at such a level that precision may be applied to the analysis of drug / substrate / inhibitor / ligandreceptor interactions, allowing the inspired structural guess regarding parameters of interplay to be complemented by the large-scale production of previously unattainable potential targets by cloning and expression techniques coupled with rapid analysis via crystallography and molecular graphic displays. The book clearly delineates, however, that the subject is in its infancy. For example, in many areas the biology of the systems being probed is essentially unresolved and therefore the inhibitor target is questionable. Thus potential inhibitory molecules are far removed from the stage of structural fine tuning for improved molecular fit as is probably best illustrated in this book by the chapter of Hitchings and