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.

The present volume of "Current Topics in Microbiology and Immunology" is a series of papers on subjects that are relevant to the growing use of 'wild mice' in immunological, microbiological and genetical research. 'Wild mice' is a jargonistic term that is used chiefly in the laboratory to refer to the naturally living forms of house mice (Mus musculus) and also other species closely related to M. musculus. This group of species is designated by systematists as the genus Mus. Immunologists began 20 years ago to study the polymorphisms of 1mmunoglobulins and major histocompatibility complex antigens in wild mice. An extrordinary extension of the highly polymorphic array of phenotypes known in inbred mice was encountered. Breeding stocks of wild mice were brought into the laboratory. This included not only M. musculus but a)so many of the available species in the genus Mus-from Southeast Asia ~nd Europe. This availability led to other comparisons of 'wild' and inbred mice and the discovery of other new and interesting phenotypes and genotypes. It became apparent that inbred strains of mice provided only a limited window for viewing the genetic diversity of Mus musculus.

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.