![]() ![]() A third major component of LLPC survival is the microenvironment/LLPC niche itself. Metabolic fitness is another key component of LLPC longevity, facilitating the diversion of glucose to generate pyruvate during times of stress to facilitate long term survival. Other potential factors include expression of BCMA, upregulation of the transcription factor ZBTB20, and upregulation of the enzyme ENPP1. ![]() PC survival in general) most notably include those that upregulate the anti-apoptotic factor Mcl-1 and activation of the CD28 receptor expressed on LLPC. LLPC are not intrinsically long-lived they require continuous signals from the LLPC niche to survive. Longevity is the hallmark of LLPC, but why and how they survive and function for years after antigen exposure is only beginning to be understood. Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United StatesÄurable humoral immunity is dependent upon the generation of antigen-specific antibody titers, produced by non-proliferating bone marrow resident long-lived plasma cells (LLPC).This triggers the immune cell to target the antibody-coated cell for lysis.Shivana M. ADCC occurs when the Fc portion of an antibody bound to the surface of a cell interacts with Fc receptor on immune cells such as macrophages, NK cells and neutrophils.Antibody-Dependent Cellular Cytotoxicity (ADCC).The complement system can also activate phagocytes to destroy bacteria that would otherwise not be recognized by the immune system. The complement cascade leads to the formation of a protein complex on bacteria that can kill the bacteria. Complement is a system of plasma proteins that can be activated by antibodies bound on a cell.When these antibodies bind to cancer cells expressing CD20 or CD52, they induce opsonization, which leads to the death of the cancer cells. Note: This is one of the main effector mechanisms responsible for the efficacy of anti-CD20 and anti-CD52 monoclonal antibodies.When a bacterium or toxin is covered with antibodies, the Fc region of these antibodies can be recognized by phagocytic cells during the process of opsonization. Antibodies contain both a Fab region, which is specific for the antigen, and an Fc region, or constant region.Neutralization occurs when antibodies bind to pathogens or toxins in order to prevent the pathogens from infecting cells.Used with permission from Macmillan Publishers Ltd: Nature 421, 440-444, copyright 2003. There are 4 main methods by which antibodies exert their effects.Antibodies bind to extracellular pathogens and toxins to mediate their destruction by phagocytic cells.When activated B cells are exposed to IFN-gamma, they undergo isotype switching to IgG2a and IgG3.When activated B cells are exposed to TGF-beta, they undergo isotype switching to IgG2b and IgA.When activated B cells are exposed to IL-4, they undergo isotype switching to IgE.Antibodies are originally of the IgM isotype.Isotype determines the effector function of the antibody.However, B cells also undergo a process called isotype switching which allows different functional classes of antibodies (i.e., IgM and IgG) to be produced that all have the same antigen specificity. B cells are similar to T cells in that they undergo somatic hypermutation to produce their antigen receptors.Used with permission from Macmillan Publishers Ltd: Nature Reviews Immunology 2, 60-65, copyright 2002. Plasma cells are B cells that secrete their antigen-specific receptors in the form of antibodies.After activation, B cells undergo rounds of mutation and selection to generate high-affinity memory B cells and plasma cells.B cells are activated by antigen presented by MHC and co-stimulatory (CD40-CD40L) signals from Th2 cells. ![]()
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