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Follicular B Helper T cells : ウィキペディア英語版 | Follicular B helper T cells Follicular B helper T cells (also known as just Follicular helper T cells or TFH), are antigen-experienced CD4+ T cells found in the periphery within B cell follicles of secondary lymphoid organs such as lymph nodes, spleens and Peyer's patches, and are identified by their constitutive expression of the B cell follicle homing receptor CXCR5. Upon cellular interaction and cross-signaling with their cognate follicular (Fo B) B cells, TFH cells trigger the formation and maintenance of germinal centers through the expression of CD40 ligand (CD40L) and the secretion of IL-21 and IL-4. TFH cells also migrate into these seeded germinal centers, predominantly composed of rapidly dividing and mutating B cells. Within germinal centers, TFH cells play a critical role in mediating the selection and survival of B cells that go on to differentiate either into special plasma cells capable of producing high affinity antibodies against foreign antigen, and memory B cells capable of quick immune re-activation in the future if ever the same antigen is re-encountered. TFH cells are also thought to facilitate negative selection of potentially autoimmune-causing mutated B cells in the germinal center. However, the biomechanisms by which TFH cells mediate germinal center tolerance are yet to be fully understood. It is possible that TFH cells might arise as branches in the Th1 and Th2 differentiation pathways but their precise lineage relationship to the other effector CD4+ T cell subsets is still uncertain. Recent studies have however shown that TFH have distinct gene expression profiles, supporting the theory that TFH are a subset of CD4+ T cells distinct from Th-1, Th-2, Th-17 or Tregs. == Biomolecular characterization == The inducible T-cell co-stimulator (''CD278'' or ''ICOS'') is proven to provide a particularly critical signal for TFH cells since experimental mice deficient in ICOS are unable to develop any TFH. Additionally, it has been shown that ICOS induces the secretion of IL-21 cytokine by activated CD4+ T cells and that IL-21 plays a crucial role in the development of TFH cells and germinal centers. Also Bcl-6 is a transcription factor identified in TFH cells, but it may have roles that extend beyond this subset, because it has also been implicated in memory CD8+ T cell development. In germinal centers, antigen-experienced TFH cells rapidly upregulate the expression of CD40L, which binds and stimulates the B cell surface receptor CD40. TFH cell-dependent paracrine activation of B cell CD40 results in B cell survival and differentiation, including the induction of AID (activation-induced (cytidine) deaminase). AID expression (encoded by the ''AICDA'' gene) causes B cell antibodies to class switch from IgM/IgD to other antibody isotypes and drives somatic hypermutation during clonal proliferation. The switched antibodies acquire better effector functions, and hypermutated antibody shows greater affinity for antigen.
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