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Molecular immunology
Cell, Vol. 55, 745-746,
December
2. 1968, Copyright
0 1988 by Cell Press
Book Reviews
“Current” Developments Ion Channels. Volume 1. By T. Narahashi. New York: Plenum Press. (1988). 334 pp. $59.50.
/on Channels is the first in a series “dealing with current developments in the study of ion channels!’ The preface fails to point out to whom the series, or this its first member, is really directed. A target audience is not immediately obvious: it is not a book for the uninitiated, but contains material of interest to researchers, postdoctoral fellows, and, perhaps, graduate students in the field. And what of the material itself? The eight contributors (there are eight chapters, some multiauthored) range widely both in the way in which they have interpreted their remits and in the audience that they seem to address. Two chapters deal with general methods to study ion channels-one is fluorescence spectroscopy and the other is the use of toxins. The chapter on fluorescence spectroscopy (Angelides) contains a useful review of the principles, but both suffer from too much technical detail. Both chapters, but most notably the one on toxins (Albuquerque et al.), contain boring tables of apparently unpublished (and perhaps unpublishable) data, which are hardly likely to enthuse strangers to the fields. The contribution by Albuquerque et al. is particularly heavy with details, containing forty-two figures (the other chapters have an average of twelve). Two chapters report on potassium channels. Brown’s contribution on the M current is typically erudite, without superfluous detail but conveying a helpful appreciation of this particular conductance. The main difficulties here are that there remains much ignorance of the single-channel properties, and this leaves the reader a little unfulfilled, and there is not much effort made to place the current in a true perspective when other cell currents (many targets of the same transmitters) are also considered. The other chapter, on potassium current sensitive to internal ATP in the heart (Noma and Shibaski), is a very well balanced mix of critical methodological points as well as a succinct review of the most important results. These two contributions are highly recommended reading. The final two chapters of the book deal with channels in epithelial tissue; one (Eaton and Hamilton) reviews the amiloride-sensitive sodium channel. Poor editing makes it a struggle for the average reader to determine whether the channels are in intestine, kidney, bladder, cell lines, bilayers, or frog skin. On the other hand, the specialist will find here a useful review of the properties of this particular set of channels. The contribution on ocular epithelium (Rae et al.) is more general, dealing with the difficulties of identifying particular channels under circumstances where several channels are commonly found in one patch. The chapter is prefaced by a particularly interesting
section on different glasses in the construction of patch clamp electrodes. Reynolds and Snyder contribute a nice review on dihydropyridine binding sites, entitled “Calcium Antagonist Receptors.” This material, unfortunately, is out of date, as it includes nothing about the amino acid sequence of the dihydropyridine binding site. Such is the problem of multiauthor books such as this one. The eighth contribution is from Kidokoro and deals with the properties of the nicotinic acetylcholine receptor during development. This clear and well-written review succeeds in guiding the reader through the various experimental findings in different species at different stages. It is refreshingly unpatronizing by comparison with other chapters (several of which start by saying what a singlechannel recording is and how it is obtained), and it is succinctly but appropriately illustrated. Overall, the kickoff of the series is a limited success. Some contributors have made a good effort to review their fields in a scholarly yet succinct manner; others have succumbed to the opportunity to present overwhelming details of their own unpublished findings. The volume appears to have been edited sparingly, if at all. If the further members of the series can attain or surpass the quality of this first volume, then the publication may deserve a place on the shelf of the libraries of those institutions with significant cadres of ion channel enthusiasts; it is unlikely to be cost-effective for the collections of individual scientists. Perhaps the best way to ensure its place even in the institutional library would be, first, more serious editing and, second, some contributions from the quite distinguished members of the editorial board of the series. Until we see the next volume or two, the impact of the series will remain sub judice. R. Alan North Vollum Institute for Advanced Biomedical Research The Oregon Health Sciences University Portland, Oregon 97201
Molecules at the Frontiers Molecular Immunology. Edited by 9. D. Hames and D. M. Glover. Oxford: IRL Press. (1988). 248 pp. $30.00.
One wonders whether the ambitious undertaking of providing a “comprehensive, up-to-date account of the major areas of progress in our understanding of the immune system” is realistic for a paperback of under 250 pages. Molecular Immunology, however, achieves this goal or at least comes very close. The recipe: to focus on five major areas (covered in five chapters) and to hire lead-
Cell 746
ing researchers in the respective fields to do the writing. The result is an excellent book, although occasionally difficult to read because the information is so condensed. The text is certainly to be highly recommended for the advanced student of immunology or researchers in related areas who wish to update their knowledge. The first chapter, by Blackwell and Alt, focuses on immunoglobulin genes and serves as a quasi-introduction to the rest of the book, presenting terms such as “clonal selection:’ “repertoire:’ and ‘allelic exclusion” for the first time. The authors ease into their topic by describing an antibody molecule, the general structure of immunoglobulin gene-related genes, and model systems for B cell differentiation. The section on the immunoglobulin superfamily, because of rapid development in this field, is already somewhat out of date. (The genes for the T cell receptor [TCR] delta chain are now known in both humans and mice, as the reader finds out in the next chapter.) Clearly, the major expertise of Fred Alt and his collaborators lies in immunoglobulin heavy-chain gene assembly, and consequently the sections dealing with this important problem are well written and very detailed. The findings described have already stimulated studies on related genes, e.g., the genes of the TCR for antigen, and on the recombinase enzymes, perhaps the most fascinating area of research in this field. I noticed that relatively little space is devoted to a phenomenon peculiar to lg genes: somatic mutation. This may in part reflect our scant knowledge, and may in part reflect the bias of the authors. Nevertheless, why is it that T cells do not undergo somatic mutation and affinity maturation, and what is the mechanism of hypermutation? The next, comparatively short chapter on T cell antigen receptor genes, by Davis, describes all four TCR genes and their expressed TCR chains. Here, changes can be expected since research in this area is still very much in progress. The best known TCR locus, the beta gene, is described in greatest detail. Included in this chapter is also a very recent focus of interest, namely, the structure and function of two new TCR genes, gamma and delta. The gamma-delta heterodimeric surface receptor molecularly defines a new subset of lymphocytes, resembling in many ways classical MHC-restricted T lymphocytes but with as yet unknown functions. The last two sections deal briefly with translocations involving TCR genes: possible oncogenie translocations and translocations in ataxia telangiectasia. It is not known how these events might contribute to neoplasia or other disorders, but this is clearly a very important area of future research. The third chapter, on MHC antigen genes, by Guillemot and colleagues, is the longest and probably most detailed (fifty pages without the references). The authors have done a remarkable job in compressing a veritable wealth of information into this space. The organization of MHC class I and class II genes is described in detail, including evolutionary aspects and the generation of polymorphism which is so important in this group of genes. Regulation of class I and class II gene expression is dealt with, and, where possible, obvious structure-function relationships are pointed out. Some bias toward human genes is notice-
able, in contrast to the bias toward mouse genes of the first two chapters. What is surprising is that some recent findings in antigen presentation, specifically the peptide binding properties of class II proteins, are not even mentioned. This rapidly developing area has provided us with crucial insight into the mechanisms of antigen presentation to T lymphocytes and consequently into the driving forces of most immune responses. The fourth chapter, by Terhorst et al., describes in molecular terms how a T lymphocyte recognizes antigen or a target cell and becomes functionally activated. The molecular structure of the TCR-CD3 complex and a number of accessory molecules, all involved in antigen-dependent pathways of T cell activation, are described, and molecules involved in antigen-independent pathways are discussed as well. The interplay between the TCR-CD3 complex and CD4 or CD8, including the possible synergism of these molecules in T cell activation, is considered, and, finally, a major section of the chapter is devoted to signal transduction. Lymphocyte activation is an active area where much progress can be expected, and which, as the authors write, “should contribute considerably to our general knowledge of signal transduction mechanisms:’ The final chapter, by Reid, on the complement system is yet another tour de force. As a nonspecialist, I was intrigued with how much has been learned in recent years about the exact gene structures of the complement components. A table covering two pages is required just to summarize all these data; only a few genes were left uncloned at the time this chapter was written, among them those encoding properdin and C8. The author points out that research is now likely to focus on the control of gene expression in this system, with the possibility of new insights into gene regulation in general. Illustrations in a chapter of this scope are essential, and the thirteen figures here are barely enough. Molecular immunology is an advanced text and, with 1094 references, is a veritable sourcebook of recent experimental data. It will be of interest and use to graduate students and researchers alike, and has the potential to evolve into an even larger, fully illustrated textbook. Willi Born Department of Pediatrics National Jewish Center for Immunology and Respiratory Medicine Denver, Colorado 80208
December
2. 1968, Copyright
0 1988 by Cell Press
Book Reviews
“Current” Developments Ion Channels. Volume 1. By T. Narahashi. New York: Plenum Press. (1988). 334 pp. $59.50.
/on Channels is the first in a series “dealing with current developments in the study of ion channels!’ The preface fails to point out to whom the series, or this its first member, is really directed. A target audience is not immediately obvious: it is not a book for the uninitiated, but contains material of interest to researchers, postdoctoral fellows, and, perhaps, graduate students in the field. And what of the material itself? The eight contributors (there are eight chapters, some multiauthored) range widely both in the way in which they have interpreted their remits and in the audience that they seem to address. Two chapters deal with general methods to study ion channels-one is fluorescence spectroscopy and the other is the use of toxins. The chapter on fluorescence spectroscopy (Angelides) contains a useful review of the principles, but both suffer from too much technical detail. Both chapters, but most notably the one on toxins (Albuquerque et al.), contain boring tables of apparently unpublished (and perhaps unpublishable) data, which are hardly likely to enthuse strangers to the fields. The contribution by Albuquerque et al. is particularly heavy with details, containing forty-two figures (the other chapters have an average of twelve). Two chapters report on potassium channels. Brown’s contribution on the M current is typically erudite, without superfluous detail but conveying a helpful appreciation of this particular conductance. The main difficulties here are that there remains much ignorance of the single-channel properties, and this leaves the reader a little unfulfilled, and there is not much effort made to place the current in a true perspective when other cell currents (many targets of the same transmitters) are also considered. The other chapter, on potassium current sensitive to internal ATP in the heart (Noma and Shibaski), is a very well balanced mix of critical methodological points as well as a succinct review of the most important results. These two contributions are highly recommended reading. The final two chapters of the book deal with channels in epithelial tissue; one (Eaton and Hamilton) reviews the amiloride-sensitive sodium channel. Poor editing makes it a struggle for the average reader to determine whether the channels are in intestine, kidney, bladder, cell lines, bilayers, or frog skin. On the other hand, the specialist will find here a useful review of the properties of this particular set of channels. The contribution on ocular epithelium (Rae et al.) is more general, dealing with the difficulties of identifying particular channels under circumstances where several channels are commonly found in one patch. The chapter is prefaced by a particularly interesting
section on different glasses in the construction of patch clamp electrodes. Reynolds and Snyder contribute a nice review on dihydropyridine binding sites, entitled “Calcium Antagonist Receptors.” This material, unfortunately, is out of date, as it includes nothing about the amino acid sequence of the dihydropyridine binding site. Such is the problem of multiauthor books such as this one. The eighth contribution is from Kidokoro and deals with the properties of the nicotinic acetylcholine receptor during development. This clear and well-written review succeeds in guiding the reader through the various experimental findings in different species at different stages. It is refreshingly unpatronizing by comparison with other chapters (several of which start by saying what a singlechannel recording is and how it is obtained), and it is succinctly but appropriately illustrated. Overall, the kickoff of the series is a limited success. Some contributors have made a good effort to review their fields in a scholarly yet succinct manner; others have succumbed to the opportunity to present overwhelming details of their own unpublished findings. The volume appears to have been edited sparingly, if at all. If the further members of the series can attain or surpass the quality of this first volume, then the publication may deserve a place on the shelf of the libraries of those institutions with significant cadres of ion channel enthusiasts; it is unlikely to be cost-effective for the collections of individual scientists. Perhaps the best way to ensure its place even in the institutional library would be, first, more serious editing and, second, some contributions from the quite distinguished members of the editorial board of the series. Until we see the next volume or two, the impact of the series will remain sub judice. R. Alan North Vollum Institute for Advanced Biomedical Research The Oregon Health Sciences University Portland, Oregon 97201
Molecules at the Frontiers Molecular Immunology. Edited by 9. D. Hames and D. M. Glover. Oxford: IRL Press. (1988). 248 pp. $30.00.
One wonders whether the ambitious undertaking of providing a “comprehensive, up-to-date account of the major areas of progress in our understanding of the immune system” is realistic for a paperback of under 250 pages. Molecular Immunology, however, achieves this goal or at least comes very close. The recipe: to focus on five major areas (covered in five chapters) and to hire lead-
Cell 746
ing researchers in the respective fields to do the writing. The result is an excellent book, although occasionally difficult to read because the information is so condensed. The text is certainly to be highly recommended for the advanced student of immunology or researchers in related areas who wish to update their knowledge. The first chapter, by Blackwell and Alt, focuses on immunoglobulin genes and serves as a quasi-introduction to the rest of the book, presenting terms such as “clonal selection:’ “repertoire:’ and ‘allelic exclusion” for the first time. The authors ease into their topic by describing an antibody molecule, the general structure of immunoglobulin gene-related genes, and model systems for B cell differentiation. The section on the immunoglobulin superfamily, because of rapid development in this field, is already somewhat out of date. (The genes for the T cell receptor [TCR] delta chain are now known in both humans and mice, as the reader finds out in the next chapter.) Clearly, the major expertise of Fred Alt and his collaborators lies in immunoglobulin heavy-chain gene assembly, and consequently the sections dealing with this important problem are well written and very detailed. The findings described have already stimulated studies on related genes, e.g., the genes of the TCR for antigen, and on the recombinase enzymes, perhaps the most fascinating area of research in this field. I noticed that relatively little space is devoted to a phenomenon peculiar to lg genes: somatic mutation. This may in part reflect our scant knowledge, and may in part reflect the bias of the authors. Nevertheless, why is it that T cells do not undergo somatic mutation and affinity maturation, and what is the mechanism of hypermutation? The next, comparatively short chapter on T cell antigen receptor genes, by Davis, describes all four TCR genes and their expressed TCR chains. Here, changes can be expected since research in this area is still very much in progress. The best known TCR locus, the beta gene, is described in greatest detail. Included in this chapter is also a very recent focus of interest, namely, the structure and function of two new TCR genes, gamma and delta. The gamma-delta heterodimeric surface receptor molecularly defines a new subset of lymphocytes, resembling in many ways classical MHC-restricted T lymphocytes but with as yet unknown functions. The last two sections deal briefly with translocations involving TCR genes: possible oncogenie translocations and translocations in ataxia telangiectasia. It is not known how these events might contribute to neoplasia or other disorders, but this is clearly a very important area of future research. The third chapter, on MHC antigen genes, by Guillemot and colleagues, is the longest and probably most detailed (fifty pages without the references). The authors have done a remarkable job in compressing a veritable wealth of information into this space. The organization of MHC class I and class II genes is described in detail, including evolutionary aspects and the generation of polymorphism which is so important in this group of genes. Regulation of class I and class II gene expression is dealt with, and, where possible, obvious structure-function relationships are pointed out. Some bias toward human genes is notice-
able, in contrast to the bias toward mouse genes of the first two chapters. What is surprising is that some recent findings in antigen presentation, specifically the peptide binding properties of class II proteins, are not even mentioned. This rapidly developing area has provided us with crucial insight into the mechanisms of antigen presentation to T lymphocytes and consequently into the driving forces of most immune responses. The fourth chapter, by Terhorst et al., describes in molecular terms how a T lymphocyte recognizes antigen or a target cell and becomes functionally activated. The molecular structure of the TCR-CD3 complex and a number of accessory molecules, all involved in antigen-dependent pathways of T cell activation, are described, and molecules involved in antigen-independent pathways are discussed as well. The interplay between the TCR-CD3 complex and CD4 or CD8, including the possible synergism of these molecules in T cell activation, is considered, and, finally, a major section of the chapter is devoted to signal transduction. Lymphocyte activation is an active area where much progress can be expected, and which, as the authors write, “should contribute considerably to our general knowledge of signal transduction mechanisms:’ The final chapter, by Reid, on the complement system is yet another tour de force. As a nonspecialist, I was intrigued with how much has been learned in recent years about the exact gene structures of the complement components. A table covering two pages is required just to summarize all these data; only a few genes were left uncloned at the time this chapter was written, among them those encoding properdin and C8. The author points out that research is now likely to focus on the control of gene expression in this system, with the possibility of new insights into gene regulation in general. Illustrations in a chapter of this scope are essential, and the thirteen figures here are barely enough. Molecular immunology is an advanced text and, with 1094 references, is a veritable sourcebook of recent experimental data. It will be of interest and use to graduate students and researchers alike, and has the potential to evolve into an even larger, fully illustrated textbook. Willi Born Department of Pediatrics National Jewish Center for Immunology and Respiratory Medicine Denver, Colorado 80208