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Discovery of the BLyS (also known as BAFF) family of ligands and receptors has yielded a paradigm shift in our view of B-lymphocyte selection, survival, activation, and homeostasis. Previously, the B-cell antigen receptor (BCR) was viewed as the sole mediator of these parameters, in which BCR signals were not only dominant but were also linearly related to consequent outcomes. However, appreciating that BLyS signaling is an equal partner in establishing and maintaining B-cell pools in- cated that additional regulatory complexity - apparently based on population density and homeostatic demands - had to be included in models of B-cell behavior. This mounting interest was ampli?ed by evidence of a clear relationship to autoim- nity. The resulting ?urry of research activity has yielded a wealth of information and insights, impacting basic concepts in B-cell tolerance and activation as well as revealing novel translational strategies for autoimmunity, neoplasia, and transplant tolerance. This book includes 12 chapters that together yield an overview of these advances and ideas. The initial excitement generated by associations with humoral autoimmunity, coupled with profound B lineage phenotypes in knockout mouse models, prompted immediate questions: What do these receptors and cytokines look like, how do they interact, what cells express them, and how does this inform our understating of their biology? Indeed, probing the structural features of BLyS family ligands and rec- tors has afforded substantial insight, as have studies directed toward understanding the basic biological actions of these molecules.
List of contents
The Beautiful Structures of BAFF, APRIL, and Their Receptors.- BAFF Receptor Regulation of Peripheral B-Lymphocyte Survival and Development.- Regulation of B-Cell Self-Tolerance By BAFF and the Molecular Basis of Its Action.- Role of BAFF and APRIL in Antibody Production and Diversification.- Signal Transduction by Receptors for BAFF and APRIL.- TACI Signaling and Its Role in Immunity.- The BAFF/APRIL System in Autoimmunity.- Systemic Immune-Based Rheumatic Diseases: Blissless States of BLySfulness.- The Role of BAFF and APRIL in Regulating Human B-Cell Behaviour: Implications for Disease Pathogenesis.- Translation of BAFF Inhibition from Mouse to Non-human Primate and Human.- BLyS/BR3 Receptor Signaling in the Biology and Pathophysiology of Aggressive B-Cell Lymphomas.- Tipping the Scales of Survival: The Role of BLyS in B-Cell Malignancies.
Summary
Discovery of the BLyS (also known as BAFF) family of ligands and receptors has yielded a paradigm shift in our view of B-lymphocyte selection, survival, activation, and homeostasis. Previously, the B-cell antigen receptor (BCR) was viewed as the sole mediator of these parameters, in which BCR signals were not only dominant but were also linearly related to consequent outcomes. However, appreciating that BLyS signaling is an equal partner in establishing and maintaining B-cell pools in- cated that additional regulatory complexity – apparently based on population density and homeostatic demands – had to be included in models of B-cell behavior. This mounting interest was ampli?ed by evidence of a clear relationship to autoim- nity. The resulting ?urry of research activity has yielded a wealth of information and insights, impacting basic concepts in B-cell tolerance and activation as well as revealing novel translational strategies for autoimmunity, neoplasia, and transplant tolerance. This book includes 12 chapters that together yield an overview of these advances and ideas. The initial excitement generated by associations with humoral autoimmunity, coupled with profound B lineage phenotypes in knockout mouse models, prompted immediate questions: What do these receptors and cytokines look like, how do they interact, what cells express them, and how does this inform our understating of their biology? Indeed, probing the structural features of BLyS family ligands and rec- tors has afforded substantial insight, as have studies directed toward understanding the basic biological actions of these molecules.
