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Lymphocyte stimulation
Cell 416
Stimulating
the Lymphocyte
Lymphocyte Stimulation, by N. R. Ling and J. E. Kay. Revised edition. Pp. 398 (American Elsevier: New York) $45.95
Lymphocyte Stimulation by N. R. Ling and J. E. Kay was first published in 1968 as a treatise on the mechanisms and consequences of stimulation of lymphocytes by a variety of predominantly biological agents. The present volume represents an effort to update the first edition. The task is extremely arduous due to the many conceptual and technical advances made during the intervening years. These advances include the purification and more precise definition of stimulating substances present in earlier crude extracts, the discovery of new stimulating substances and protocols, and a more detailed knowledge of the composition of lymphocyte populations, based largely on investigations of the immunogenetics and receptor properties of the lymphocyte cell surfaces. The most useful contribution of the book is its overall concern with the biology of lymphocyte stimulation. This includes the description of experimental configurations and lymphocyte populations used, parameters monitored as indices of stimulation, and stimulating substances and protocols studied. The reader who is well schooled in immunology is able to survey the many facets of lymphocyte stimulation in one volume. A major problem with writing a treatise on an immunological subject as complex as lymphocyte stimulation is the enormous variety of species, lymphocyte populations, and protocols and preparations used for stimulation. Knowledge of the immunological status of the lymphocyte donors (for example, immunized, unimmunized, or possessing “natural immunity”) is also of considerable importance in evaluating the results of a particular stimulating protocol. Moreover, when dealing with complex lymphocyte populations, it is necessary to distinguish primary stimulation of a cell resulting from direct action of the stimulus upon it, and secondary recruitment of bystander cells which can occur indirectly as a result of the stimulation of their companions. The authors are keenly aware of these problems, and their careful organization of the text and references allows the knowledgeable reader easy access to a sub-area of interest. Moreover, their chapter on methods of culturing lymphocytes provides an excellent account of the protocols used and the experimental variables which must be considered in studying lymphocytes in culture. Nearly all of this information is described in the text, and this points up a major limitation of the book as a
whole. The number of figures and tables is extremely small, and those included represent data communication. The density of the text as well as the lack of didactic figures and tables restrict the audience to those deeply involved in the field and will serve to discourage the more casual but interested reader. The authors point out pitfalls in experimental approaches and conclusions wherever possible, and the conclusion is inescapable that far too often experiments have not been tightly enough conceived or controlled. Ling and Kay are critical of conclusions drawn from studies performed on different species and cell populations, and point out the problems in interpretation of experiments performed with stimulating reagents of varying degrees of purity. They correctly emphasize that for elucidation of growth control mechanisms ‘I. . the growth stimulant should be a defined and traceable molecule.” Moreover, care must be taken in distinguishing macromolecular and metabolic alterations which constitute part of the mechanism of the activation process from artifacts which may result, for example, from activation-associated changes in the permeability of lymphocytes to isotopic tracers used in the assay for stimulation. The descriptions of the biology of lymphocyte stimulation and the parameters studied are extremely useful. However, a number of arguments concerning the nature of particular cell surface receptors and their putative role in immune phenomena in vivo appear to reflect the authors’ prejudices and are not adequately justified in the text. For example, in discussing antigen suicide experiments (p. 183), they state that it is improbable that a lymphocyte reacts to only one antigen. Also, a line of reasoning is presented (pp. 193-195) involving the existence of H-P-linked immune response genes in the mouse, which leads to the suggestion that the immunoglobulin on B cells is not the primary receptor for antigen on these cells. These and other theoretical considerations are not thoroughly discussed, and although they are of considerable interest and merit further discussion, their inclusion almost as an aside detracts from the more scholarly and complete treatment of the experimental aspects of lymphocyte stimulation. An unfortunate limitation of the book is the rather cursory discussion of the I region which maps within the major histocompatibility complex (H-2 complex) of the mouse. Immune response genes (Ir genes) and genes determining lymphocyte surface antigens (la antigens) have been mapped in this region, and it is probable that their characterization will shed considerable light on the mechanisms of activation of lymphocytes by other lymphocytes (for example, in the mixed leucocyte reaction) and by
Book 417
Reviews
Evolution
antigen in the immune response. The significant advances made in this area during 1974 and 1975 may have been reported too late for inclusion in this volume. As a whole, the revised edition of Lymphocyte Stimulation constitutes an enormously useful window to the biology of lymphocyte stimulation for the knowledgeable immunologist or cell biologist. Elucidation of the mechanisms by which lymphocytes are activated is the object of intense research activity at this time, and new developments are emerging at an astounding rate. The wealth of material presented in this volume is therefore timely and of great interest and usefulness to the active researcher. Paul D. Gottlieb Department of Biology and Center for Cancer Research Massachusetts institute of Technology Cambridge, Massachusetts
of Molecules
Comparative Biology, Molecular Evolution, volume 29B in the series Comprehensive Biochemistry, edited by M. Florkin and E. H. Stotr. Pp. 328. (American Elsevier: New York). $31.25
This volume represents the other three of the five chapters on molecular evolution that are part of the extensive treatise on comparative biochemistry. The previous volume (29A) was reviewed in Cell 3, 384 (1974). The first chapter, by J. de Ley and K. Kersters addresses biochemical evolution in bacteria. It seemed to me to be comprehensive in the sense of covering all the significant molecular sources of understanding, including the distribution of small molecules, cell wall characteristics, metabolic pathways, proteins (both sequence and electrophoretic differences), and DNA hybridization. Anyone familiar with only one of these areas will be intrigued by ideas stimulated by a consideration of the others. The last two chapters are by Dr. Florkin. The first of these is on animal evolution and completes the triad on plant, animal, and bacterial evolution. It has two major divisions, representing macromolecular sequences and small molecules. The latter section covers the original literature rather extensively, although the great mass of data in the field has forced selectivity in the presentation. I came away with the feeling that there were many interesting evolutionary problems to solve but that few, if any, major phylogenetic issues. at the higher taxa levels have been or will be decided from such comparative studies of small molecules. The macromolecular sequence section was nearly twice as long but had barely more than half as many references, suggesting some haste in its formulation since Dr. Florkin is something of a bibliophile. The result is a section that, rather than covering the original literature, is largely drawn from Dayhoff’s Atlas of Protein Sequences (vol. 5) with interesting commentary on points relating to her alignments and phylogenies. More than 20 pages are devoted to a reproduction of alignments that can be found in the atlas. Many outstanding contributors of the facts, theories, and excitement of this field have been almost completely ignored. The last chapter is on prebiological evolution. It is very short (27 pp.), largely historical, and focused primarily on the Oparin-Miller-Fox schools of thought. The readability of these two chapters is considerably greater than that noticed in the previous volume, and only occasionally does one struggle with “protein diachronic epigenesis has been at the ori-
Stimulating
the Lymphocyte
Lymphocyte Stimulation, by N. R. Ling and J. E. Kay. Revised edition. Pp. 398 (American Elsevier: New York) $45.95
Lymphocyte Stimulation by N. R. Ling and J. E. Kay was first published in 1968 as a treatise on the mechanisms and consequences of stimulation of lymphocytes by a variety of predominantly biological agents. The present volume represents an effort to update the first edition. The task is extremely arduous due to the many conceptual and technical advances made during the intervening years. These advances include the purification and more precise definition of stimulating substances present in earlier crude extracts, the discovery of new stimulating substances and protocols, and a more detailed knowledge of the composition of lymphocyte populations, based largely on investigations of the immunogenetics and receptor properties of the lymphocyte cell surfaces. The most useful contribution of the book is its overall concern with the biology of lymphocyte stimulation. This includes the description of experimental configurations and lymphocyte populations used, parameters monitored as indices of stimulation, and stimulating substances and protocols studied. The reader who is well schooled in immunology is able to survey the many facets of lymphocyte stimulation in one volume. A major problem with writing a treatise on an immunological subject as complex as lymphocyte stimulation is the enormous variety of species, lymphocyte populations, and protocols and preparations used for stimulation. Knowledge of the immunological status of the lymphocyte donors (for example, immunized, unimmunized, or possessing “natural immunity”) is also of considerable importance in evaluating the results of a particular stimulating protocol. Moreover, when dealing with complex lymphocyte populations, it is necessary to distinguish primary stimulation of a cell resulting from direct action of the stimulus upon it, and secondary recruitment of bystander cells which can occur indirectly as a result of the stimulation of their companions. The authors are keenly aware of these problems, and their careful organization of the text and references allows the knowledgeable reader easy access to a sub-area of interest. Moreover, their chapter on methods of culturing lymphocytes provides an excellent account of the protocols used and the experimental variables which must be considered in studying lymphocytes in culture. Nearly all of this information is described in the text, and this points up a major limitation of the book as a
whole. The number of figures and tables is extremely small, and those included represent data communication. The density of the text as well as the lack of didactic figures and tables restrict the audience to those deeply involved in the field and will serve to discourage the more casual but interested reader. The authors point out pitfalls in experimental approaches and conclusions wherever possible, and the conclusion is inescapable that far too often experiments have not been tightly enough conceived or controlled. Ling and Kay are critical of conclusions drawn from studies performed on different species and cell populations, and point out the problems in interpretation of experiments performed with stimulating reagents of varying degrees of purity. They correctly emphasize that for elucidation of growth control mechanisms ‘I. . the growth stimulant should be a defined and traceable molecule.” Moreover, care must be taken in distinguishing macromolecular and metabolic alterations which constitute part of the mechanism of the activation process from artifacts which may result, for example, from activation-associated changes in the permeability of lymphocytes to isotopic tracers used in the assay for stimulation. The descriptions of the biology of lymphocyte stimulation and the parameters studied are extremely useful. However, a number of arguments concerning the nature of particular cell surface receptors and their putative role in immune phenomena in vivo appear to reflect the authors’ prejudices and are not adequately justified in the text. For example, in discussing antigen suicide experiments (p. 183), they state that it is improbable that a lymphocyte reacts to only one antigen. Also, a line of reasoning is presented (pp. 193-195) involving the existence of H-P-linked immune response genes in the mouse, which leads to the suggestion that the immunoglobulin on B cells is not the primary receptor for antigen on these cells. These and other theoretical considerations are not thoroughly discussed, and although they are of considerable interest and merit further discussion, their inclusion almost as an aside detracts from the more scholarly and complete treatment of the experimental aspects of lymphocyte stimulation. An unfortunate limitation of the book is the rather cursory discussion of the I region which maps within the major histocompatibility complex (H-2 complex) of the mouse. Immune response genes (Ir genes) and genes determining lymphocyte surface antigens (la antigens) have been mapped in this region, and it is probable that their characterization will shed considerable light on the mechanisms of activation of lymphocytes by other lymphocytes (for example, in the mixed leucocyte reaction) and by
Book 417
Reviews
Evolution
antigen in the immune response. The significant advances made in this area during 1974 and 1975 may have been reported too late for inclusion in this volume. As a whole, the revised edition of Lymphocyte Stimulation constitutes an enormously useful window to the biology of lymphocyte stimulation for the knowledgeable immunologist or cell biologist. Elucidation of the mechanisms by which lymphocytes are activated is the object of intense research activity at this time, and new developments are emerging at an astounding rate. The wealth of material presented in this volume is therefore timely and of great interest and usefulness to the active researcher. Paul D. Gottlieb Department of Biology and Center for Cancer Research Massachusetts institute of Technology Cambridge, Massachusetts
of Molecules
Comparative Biology, Molecular Evolution, volume 29B in the series Comprehensive Biochemistry, edited by M. Florkin and E. H. Stotr. Pp. 328. (American Elsevier: New York). $31.25
This volume represents the other three of the five chapters on molecular evolution that are part of the extensive treatise on comparative biochemistry. The previous volume (29A) was reviewed in Cell 3, 384 (1974). The first chapter, by J. de Ley and K. Kersters addresses biochemical evolution in bacteria. It seemed to me to be comprehensive in the sense of covering all the significant molecular sources of understanding, including the distribution of small molecules, cell wall characteristics, metabolic pathways, proteins (both sequence and electrophoretic differences), and DNA hybridization. Anyone familiar with only one of these areas will be intrigued by ideas stimulated by a consideration of the others. The last two chapters are by Dr. Florkin. The first of these is on animal evolution and completes the triad on plant, animal, and bacterial evolution. It has two major divisions, representing macromolecular sequences and small molecules. The latter section covers the original literature rather extensively, although the great mass of data in the field has forced selectivity in the presentation. I came away with the feeling that there were many interesting evolutionary problems to solve but that few, if any, major phylogenetic issues. at the higher taxa levels have been or will be decided from such comparative studies of small molecules. The macromolecular sequence section was nearly twice as long but had barely more than half as many references, suggesting some haste in its formulation since Dr. Florkin is something of a bibliophile. The result is a section that, rather than covering the original literature, is largely drawn from Dayhoff’s Atlas of Protein Sequences (vol. 5) with interesting commentary on points relating to her alignments and phylogenies. More than 20 pages are devoted to a reproduction of alignments that can be found in the atlas. Many outstanding contributors of the facts, theories, and excitement of this field have been almost completely ignored. The last chapter is on prebiological evolution. It is very short (27 pp.), largely historical, and focused primarily on the Oparin-Miller-Fox schools of thought. The readability of these two chapters is considerably greater than that noticed in the previous volume, and only occasionally does one struggle with “protein diachronic epigenesis has been at the ori-