Signal Transduction and the Coordination of B Lymphocyte Development and Function I


Book Description

Proper development and differentiation of B lymphocytes is es sential to ensure that an organism has the ability to mount an effective humoral immune response against foreign antigens. The immune system must maintain a balance between the deletion of harmful self-reactive B cells and the generation of a diverse rep ertoire of B cells that has the ability to recognize an almost un limited array of foreign antigens. The need to delete self-reactive cells is tempered by the need to avoid the generation of large functional holes in the repertoire of foreign antigen-specific B cells that patrol the periphery. To accomplish this, the immune system must reach a compromise by eliminating only the most dangerous autoreactive clones, while allowing less harmful au toreactive B cells to exist in the periphery where they may com plement the organism's ability to mount a rapid response against invading micro-organisms. Those autoreactive cells that do enter the peripheral pool are subject to a number of conditional re straints that effectively attenuate their ability to respond to self antigens. Deleterious alterations in the homeostasis between tolerance induction and recruitment of B cells into the functional repertoire may lead to increased susceptibility to autoimmune disease or infection, respectively. Therefore, delineation of the molecular processes that maintain immunological homeostasis in the B cell compartment is critical.




Signal Transduction and the Coordination of B Lymphocyte Development and Function II


Book Description

This volume provides a review of current research in the field of B cell development and differentiation with particular emphasis on signal transduction processes. The volume is divided into two parts that focus, respectively, on the basic biochemical pathways which regulate B cell biology and the role of signal transduction processes in regulating various aspects of B cell function, development and differentiation. In this second part the molecular processes involved in translating BCR engagement to specific biological outcomes are reviewed. Topics covered in this part include signal transduction via the pre-B cell antigen receptor complex, the control of immunoglobulin gene recombination and allelic exclusion, and molecular regulation of positive and negative selection. These latter chapters present information regarding processes which are critical for the B cell response to foreign antigen that leads to differentiation into antibody secreting plasma.













Signal Transduction and the Coordination of B Lymphocyte Development and Function I


Book Description

Proper development and differentiation of B lymphocytes is es sential to ensure that an organism has the ability to mount an effective humoral immune response against foreign antigens. The immune system must maintain a balance between the deletion of harmful self-reactive B cells and the generation of a diverse rep ertoire of B cells that has the ability to recognize an almost un limited array of foreign antigens. The need to delete self-reactive cells is tempered by the need to avoid the generation of large functional holes in the repertoire of foreign antigen-specific B cells that patrol the periphery. To accomplish this, the immune system must reach a compromise by eliminating only the most dangerous autoreactive clones, while allowing less harmful au toreactive B cells to exist in the periphery where they may com plement the organism's ability to mount a rapid response against invading micro-organisms. Those autoreactive cells that do enter the peripheral pool are subject to a number of conditional re straints that effectively attenuate their ability to respond to self antigens. Deleterious alterations in the homeostasis between tolerance induction and recruitment of B cells into the functional repertoire may lead to increased susceptibility to autoimmune disease or infection, respectively. Therefore, delineation of the molecular processes that maintain immunological homeostasis in the B cell compartment is critical.




Lymphocyte Development


Book Description

"Lymphocyte Development" presents an extremely up-to-date account of molecular processes involved in the development of lymphocytes. This well written book is based on a graduate course taught by the author. Topics include the selection processes involved in lymphocyte maturation, immune receptor gene rearrangement, signaling pathways involved in cell cycle progression and apoptosis, and the transcriptional regulation of lymphoid ontogeny. The book also covers T cell development and differentiation of helper and cytotoxic T cells as well as the development of Natural Killer lymphocytes. The book finishes with an account of the molecular basis of immunodeficiency syndromes. It will interest researchers in immunology and it will be useful as a supplementary text for a graduate level immunology course.




Mechanisms of Lymphocyte Activation and Immune Regulation V


Book Description

Signaling through antigen receptor initiates a complex series of events resulting in the activation of genes that regulate the development, proliferation and differentiation of lymphocytes. During the past few years, rapid progress has been made in understanding the molecular basis of signaling pathways mediated by antigen and cytokine receptors. These pathways involve protein tyrosine kinases which are coupled to downstream regulatory molecules, including small guanine nucleotide binding proteins (e. g. p21'OS), serine threonine kinases (e. g. , members of the ERK family), and a large group of transcription factors. More recently, there have been breakthroughs in elucidating the genetic defects underlying three X-linked primary immunodeficiency diseases in humans. This volume surveys aspects of these rapidly developing areas of research. The book is divided into 5 different sections. Section I deals with signaling pathways in B lymphocytes. It includes a contemporary assessment of B cell antigen receptor structures, and discussion of the role of Ig-a/lg-B polypeptides in linking the antigen receptor to intracellular signal transduction pathways. The role of accessory molecules in the regulation of signaling by the B cell antigen receptor is also considered. Section II adopts a similar approach to the analysis of the antigen receptor on T lymphocytes. The importance of specialized signaling motifs in the CD3 polypeptides, mechanisms whereby these motifs may interact with the lymphocyte-specific protein tyrosine kinases, and the downstream consequences of these interactions are reviewed. In addition, the role of antigen-induced apoptosis in the generation of immunological tolerance is discussed.




Mechanisms of Lymphocyte Activation and Immune Regulation IV


Book Description

In recent years rapid progress has been made in the areas of T cell and B cell biology, cell-cell and cell-matrix/stroma interactions. The use of isolated subunits of the T cell receptor invariant chains has been instrumental in defining their role in signal transduction and tyrosine phosphorylation. A role of src family phosphotyrosine kinases in T cell activation has been demonstrated and several phosphotyrosine kinase substrates have been identified and their functions characterized. Homologous recombinant techniques have led to the development of murine strains that lack CD4 or CD8 expression. These models are likely to be instrumental in studying the role of T cell subsets in autoimmune disorders, tissue transplant rejection and tumor rejection. A role of major histocompatibility complex I in the development of T cell subsets and NK cells has been defined. Recent data suggest a role of interaction between plasma membrane molecules of activated T helper cells and B cells, B cells primed with plasma membrane of activated T helper cells and cytokines, and interaction between bone marrow stromal cells and B cell progenitors and precursors, in the B cell development, proliferation, and differentiation. The structure and functions of adhesion molecules, especially with regard to signal transduction and homing events, are better defined.