Activation of B cells B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the

cell-mediated immune response, which is governed by T cells). The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells (APCs) and eventually develop into memory B cells after activation by antigen interaction. B cells are an essential component of the adaptive immune system. The abbreviation "B", in B cell, comes from the bursa of Fabricius in birds, where they mature. In mammals, immature B cells are formed in the bone marrow, which is used as a backronym for the cells' name. Development of B cells Immature B cells are produced in the bone marrow of most mammals. Rabbits are an exception; their B cells develop in the appendix-sacculus rotundus. After reaching the IgM+ immature stage in the bone marrow, these immature B cells migrate to the spleen, where they are called transitional B cells, and some of these cells differentiate into mature B lymphocytes.[2] B cell development occurs through several stages, each stage representing a change in the genome content at the antibody loci. An antibody is composed of two identical light (L) and two identical heavy (H) chains, and the genes specifying them are found in the 'V' (Variable) region and the 'C' (Constant) region. In the heavy-chain 'V' region there are three segments; V, D and J, which recombine randomly, in a process called VDJ recombination, to produce a unique variable domain in the immunoglobulin of each individual B cell. Similar rearrangements occur for light-chain 'V' region except there are only two segments involved; V and J. The list below describes the process of immunoglobulin formation at the different stages of B cell development. When the B cell fails in any step of the maturation process, it will die by a mechanism called apoptosis, here called clonal deletion.[5] B cells are continuously produced in the bone marrow. When B cell receptors on the surface of the cell matches the detected antigens present in the body, the B cell proliferates and secretes a free form of those receptors (antibodies) with identical binding sites as the ones on the original cell surface. After activation, the cell proliferates and B memory cells would form to recognise the same antigen. This information would then be used as a part of the adaptive immune system for a more efficient and more powerful immune response for future encounters with that antigen. B cell membrane receptors evolve and change throughout the B cell life span.[6] TACI, BCMA and BAFF-R are present on both immature B cells and mature B cells. All of these 3 receptors may be inhibited by Belimumab. CD20 is expressed on all stages of B cell development except the first and last; it is present from pre-pre B cells through memory cells, but not on either pro-B cells or plasma cells. Recognition of antigen by B cells

meaning T cell help is required for maximal antibody production. Activation of B cells B cell recognition of antigen is not the only element necessary for B cell activation (a combination of clonal proliferation and terminal differentiation into plasma cells). and type 2 T cell-independent activation (in which macrophages present several of the same antigen in a way that causes cross-linking of antibodies on the surface of B cells). that particular B cell will usually no longer make the earlier isotypes. T cell-dependent activation Once a pathogen is ingested by an antigen-presenting cell such as a macrophage or dendritic cell. responding with IgM synthesis in the absence of T cell help. In contrast. resulting in the proliferation and differentiation to effector and memory T cells. Isotype switching to IgG. can be activated in a T cell-dependent or -independent manner. the pathogen's proteins are then digested to peptides and attached to a class II MHC protein. Activated B cells subsequently produce antibodies which assist in inhibiting pathogens until phagocytes (i.e. Type 1 T cell-independent (polyclonal) activation. These cytokines trigger B cell proliferation and differentiation into plasma cells. macrophages. the T cell secretes cytokines that activate the B cell. T dependent antigens contain proteins that are presented on B cell Class II MHC to a special subtype of T cell called a Th2 cell. With a Tdependent antigen. and IgE and memory cell generation occur in response to T-dependent antigens. T cell-independent activation Many antigens are T cell-independent in that they can deliver both of the signals to the B cell. There are two types of T cell independent activation. also known as naïve B cells. the first signal comes from antigen cross linking the B cell receptor (BCR) and the second signal comes from co-stimulation provided by a T cell. as a peptide fragment presented by an antigen presenting cell's MHC molecule to the T cell receptor.e. The macrophage is now activated to deliver multiple signals to a specific T cell that recognizes the peptide presented. IgA. IgM or IgD. This complex is then moved to the outside of the cell membrane.A critical difference between B cells and T cells is how each lymphocyte recognizes its antigen. Most antigens are T-dependent. When a B cell processes and presents the same antigen to the primed Th cell. Mice without a thymus (nude or athymic mice that do not produce any T cells) can respond to T independent antigens. CD4+ T cells) then activate specific B cells through a phenomenon known as an Immunological synapse. . Once this switch has occurred. T cells recognize their cognate antigen in a processed form. The T cell is then stimulated to produce autocrines (Refer to Autocrine signalling). by cross-linking the IgM antigen receptors in the B cell. Helper T cells (i. neutrophils) or the complement system for example clears the host of the pathogen(s). They recognize free (soluble) antigen in the blood or lymph using their BCR or membrane bound-immunoglobulin. B cells recognize their cognate antigen in its native form. B cells that have not been exposed to antigen. Many bacteria have repeating carbohydrate epitopes that stimulate B cells. This isotype switching is known as Class Switch Recombination (CSR).

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