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.




B Cell Receptor Signaling


Book Description

This volume details our current understanding of the architecture and signaling capabilities of the B cell antigen receptor (BCR) in health and disease. The first chapters review new insights into the assembly of BCR components and their organization on the cell surface. Subsequent contributions focus on the molecular interactions that connect the BCR with major intracellular signaling pathways such as Ca2+ mobilization, membrane phospholipid metabolism, nuclear translocation of NF-kB or the activation of Bruton’s Tyrosine Kinase and MAP kinases. These elements orchestrate cytoplasmic and nuclear responses as well as cytoskeleton dynamics for antigen internalization. Furthermore, a key mechanism of how B cells remember their cognate antigen is discussed in detail. Altogether, the discoveries presented provide a better understanding of B cell biology and help to explain some B cell-mediated pathogenicities, like autoimmune phenomena or the formation of B cell tumors, while also paving the way for eventually combating these diseases.




Signaling Mechanisms Regulating T Cell Diversity and Function


Book Description

T cells play a vital role mediating adaptive immunity, a specific acquired resistance to an infectious agent produced by the introduction of an antigen. There are a variety of T cell types with different functions. They are called T cells, because they are derived from the thymus gland. This volume discusses how T cells are regulated through the operation of signaling mechanisms. Topics covered include positive and negative selection, early events in T cell receptor engagement, and various T cell subsets.




Molecular Biology of B Cells


Book Description

Molecular Biology of B Cells, Second Edition is a comprehensive reference to how B cells are generated, selected, activated and engaged in antibody production. All of these developmental and stimulatory processes are described in molecular, immunological, and genetic terms to give a clear understanding of complex phenotypes. Molecular Biology of B Cells, Second Edition offers an integrated view of all aspects of B cells to produce a normal immune response as a constant, and the molecular basis of numerous diseases due to B cell abnormality. The new edition continues its success with updated research on microRNAs in B cell development and immunity, new developments in understanding lymphoma biology, and therapeutic targeting of B cells for clinical application. With updated research and continued comprehensive coverage of all aspects of B cell biology, Molecular Biology of B Cells, Second Edition is the definitive resource, vital for researchers across molecular biology, immunology and genetics.







Cell Biology of the B Cell Receptor


Book Description

Advances in Immunology, a long-established and highly respected publication, presents current developments as well as comprehensive reviews in immunology. Articles address the wide range of topics that comprise immunology, including molecular and cellular activation mechanisms, phylogeny and molecular evolution, and clinical modalities. Edited and authored by the foremost scientists in the field, each volume provides up-to-date information and directions for the future. - Contributions from leading authorities - Informs and updates on all the latest developments in the field




PI3K signalling


Book Description

The PI3Ks control many key functions in immune cells. PI3Ks phosphorylate PtdIns(4,5)P2 to yield PtdIns(3,4,5)P3. Initially, PI3K inhibitors such as Wortmannin, LY294002 and Rapamycin were used to establish a central role for Pi3K pathway in immune cells. Considerable progress in understanding the role of this pathway in cells of the immune system has been made in recent years, starting with analysis of various PI3K and Pten knockout mice and subsequently mTOR and Foxo knockout mice. Together, these experiments have revealed how PI3Ks control B cell and T cell development, T helper cell differentiation, regulatory T cell development and function, B cell and T cell trafficking, immunoglobulin class switching and much, much more. The PI3Kd inhibitor idelalisib has recently been approved for the treatment of B cell lymphoma. Clinical trials of other PI3K inhibitors in autoimmune and inflammatory diseases are also in progress. This is an opportune time to consider a Research Topic considering when what we have learned about the PI3K signalling module in lymphocyte biology and how this is making an impact on clinical immunology and haematology.




Signal Transduction in Cancer


Book Description

One of the most exciting areas of cancer research now is the development of agents which can target signal transduction pathways that are activated inappropriately in malignant cells. The understanding of the molecular abnormalities which distinguish malignant cells from their normal counterparts has grown tremendously. This volume summarizes the current research on the role that signal transduction pathways play in the pathogenesis of cancer and how this knowledge may be used to develop the next generation of more effective and less toxic anticancer agents. Series Editor comments: "The biologic behavior of both normal and cancer cells is determined by critical signal transduction pathways. This text provides a comprehensive review of the field. Leading investigators discuss key molecules that may prove to be important diagnostic and/or therapeutic targets."