The understanding of B cell biology has increased and expanded enormously in the last three decades. It is now known that B cells, in addition to just differentiating into antibody-secreting cells, serve many other vital functions. For example, their roles as antigen-presenting cells and cytokine-producing cells as well as effector cells and regulatory cells are well appreciated now. Indeed, the pathologic role of B cells in many autoimmune disorders may be largely autoantibody-independent. Today, the B cell is of considerable interest not only to immunologists but also to mainstream clinicians and scientists. The current volume covers the latest information on the functions of B cells in normal and disease states, and their therapeutic antagonism. Chapters cover cutting-edge topics from the basic to the clinical, including B cells in infection and autoimmunity, CD19-CD21 signal transduction complex, marginal zone B cell physiology and disease, B cell growth and differentiation, their role in rheumatoid arthritis, SLE treatment, the BAFF/APRIL system and B lymphocyte malignancies. This book is recommended reading for cellular and molecular immunologists as well as for rheumatologists, hematologists and clinical immunologists, and all those interested in human diseases in which B cells play an important contributory role.

This book provides a detailed overview of B-cell directed therapies in patients with rheumatic and systemic autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, ANCA-associated vasculitis and cryoglobulinemia. Organ-specific autoimmune diseases are discussed with respect to the use of B-cell directed therapies in neurological autoimmune diseases and autoimmune cytopenias. Situations in which B-cell targeted therapy may be indicated are identified, thereby offering comprehensive support for therapeutic decisions on the basis of the latest published evidence. The book also offers a valuable reference tool for rheumatologists, internists, nephrologists, immunologists, and all specialists involved in the multidisciplinary care of patients with rheumatic and systemic autoimmune diseases.

B cells play a central role not only in adaptive immunity, but also in autoimmunity. To understand how B cells are normally prevented from reacting to self-tissue, what goes wrong in autoimmunity, and how B cells contribute to it is the aim of this book. This volume includes more than a dozen in-depth reviews by researchers specializing in various aspects of basic B cell biology that have relevance to autoimmune diseases. These up-to-date chapters present the latest information on B cell signal transduction, apoptosis, genetics and molecular biology. Also featured are chapters with special reference to particular autoimmune diseases in which B cells have been shown to play a critical role, such as type 1 diabetes, chronic graft-versus-host disease and lupus erythematosus. Further topics covered include the role of the complement system, rheumatoid factors, and anti-DNA autoantibodies as well as important related areas such as natural autoantibodies, B cell immune tolerance, Toll receptor signaling, and the immunobiology of BAFF/BLyS. Both basic researchers and clinician scientists who wish to understand the role of B lymphocytes in immune tolerance and autoimmunity will benefit from this timely publication.

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.

This book contains twelve chapters contributed by prestigious international experts who are at the forefront of B cell research, and aims to provide a cutting-edge and comprehensive overview of all aspects of B cells, including B cell development, maturation and activation, germinal center reaction, memory and plasma cell differentiation, and antibody-mediated positive and negative regulation of humoral immune responses. There are also three chapters describing human diseases caused by B cell abnormalities, including primary antibody deficiencies, autoimmune diseases, and B cell malignancies. We hope that this book will become a standard and routine reference for both basic researchers and clinicians.

Alterations in B cell homeostasis drive pathogenesis of various immune mediated diseases. Breaks in peripheral tolerance allow autoreactive B cells to differentiate in to pathogenic auto-antibody secreting cells. B cells themselves may directly drive pathogenesis through antigen-presentation capabilities and secretion of pro-fibrotic factors. Lastly, the inability of B cells to mount effective responses against pathogens may trigger subsequent inflammatory or autoimmune reactions. In this work, we dissect various ways in which B cells contribute to pathogenesis of inflammatory disease by evaluating their role in three different immune mediated diseases. In chapter 2 we identify a potential regulatory role for B cells in the context of Systemic Lupus Erythematosus (SLE), an autoimmune disease characterized by the pathogenic secretion of anti-nuclear antibodies. We found that CD52 is a B cell regulatory glycoprotein elevated on the surface of B cells in patients and acts to suppress B cell hyperactivity both through its surface expression and through the secretion of a soluble form that can bind receptor Siglec-10. In chapter 3 we describe a population of B cells that is significantly expanded in IgG4-RD, a fibroinflammatory condition characterized by infiltration of IgG4+ plasma cells into tumefactive lesions and the development of storiform fibrosis. The expanded population of B cells was CD21-- and CXCR5+, expressing high levels of pathogenic B cell marker CD11c. Moreover, the frequency of this expanded population correlated with clinical parameters such as IgG4 titers. We observed a tremendous elevation of CXCL13, the ligand for CXCR5, strongly implicating the CXCR5-CXCL13 axis in recruiting B cells to affected tissue, making it a viable therapeutic target. Lastly, in chapter 4 we performed high-dimensional sequencing on B cells from sarcoidosis patients, a disease characterized by spontaneous granuloma formation. Although B cells have not been directly implicated in the inflammation, we observed a less diverse and less mutated B cell receptor repertoire; together, our findings point to the initiation of sarcoidosis after ineffective antibody mediated clearance of pathogen from affected organs. In total, this work sheds novel insights on the role of B cells-- from the initial stages of activation and germinal center recruitment, to the development of a diverse antibody repertoire-- in the context of poorly understood immune mediated conditions and contributes important knowledge for the advancement of better treatments for affected patients.

During the past two decades, cells of the B-lymphocyte lineage have been the subject of intensive research. B-lymphocytes and antibodies play a crucial role in the body's defense against infection, but can also be responsible for producing certain diseases. This volume provides an up-to-date discussion of the cellular and molecular biology of antibodies and the cells that produce them. Researchers discuss the fundamentals of B-cell biology that are crucial to understanding how cells and their antibody products generate a range of malignant, autoimmune and immunodeficiency disorders. The discussion of human diseases in the second part of the book provides an interface between recent advances in B-cell biology and B-cell related disease processes.

A large number of diseases affect salivary gland (SG) secretion through different mechanisms, leading to SG dysfunction and associated oral problems. The glands may suffer from viral, bacterial, and, albeit rarely, fungal infections, which may cause painful swelling or obstruction; they could also become the target of an autoimmune attack or may be affected by various benign and malignant tumors which consist of a heterogeneous group of lesions with complex clinical–pathological characteristics. The loss of normal SG function results in widespread deterioration of oral health. This book, entitled “Diseases of Salivary Glands”, provides an overview of recent advances in the field of SG disorders, focusing on the cellular and molecular mechanisms involved in the pathogenesis of SG diseases and on the most innovative investigation techniques that could help to preserve patients’ health, function, and quality of life.

This book explains the immunology of organ-specific malignancies and discusses novel immunotherapy strategies for their treatment. Since the first, very successful edition of the book was published in 2015, a number of entirely new chapters have been included. The range of cancers considered has accordingly been extended, with coverage of the latest immunotherapy approaches for cancers in different organs. In addition, the original chapters have been updated to document the latest advances in immunotherapy for pediatric solid tumors, hematologic malignancies, gastrointestinal tumors, bone tumors, central nervous tumors, lung cancer, genitourinary tract tumors, and breast cancer, among others. The book is published as part of the three-volume Springer series Cancer Immunology, which aims to provide an up-to-date, clinically relevant review of cancer immunology and immunotherapy. Other volumes in the series address the translational medicine context and bench to bedside immunotherapy. Cancer Immunology: Cancer Immunotherapy for Organ-Specific Tumors will be of special value to clinical immunologists, hematologists, and oncologists.