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B lymphocytes and Humoral Immune ResponseLie Wang (汪洌)浙江省杭州市浙江大学紫金港校区医学院科研楼A810-814医学院免疫学研究所The discovery of B cell immunity1954 - Bruce Glick, Ohio State UniversityStudies on the function of the bursa of Fabricius, a lymphoid organ in the cloacal region of the chickenBursa was later found to be the organ in which antibody producing cells developed – antibody producing cells were thereafter called B cellsMammals do not have a bursa of FabriciusMature markedB cellsin peripheryTransfer marked foetalliver cellsNormal bone marrowNo MatureB cellsDefective bone marrowOrigin of B cells and organ of B cellmaturationB cell development starts in the foetal liverAfter birth, development continues in the bone marrowRegulates construction of an antigen receptorBBBBBEnsures each cell has only one specificityChecks and disposes of self-reactive B cellsExports useful cells to the peripheryProvides a site for antibody productionB cell development in the bone marrowBone Marrow provides aMATURATION DIFFERENTIATION MICROENVIRONMENTfor B cell development1. Specific cell-cell contacts between stromal cells and developing B cells2. Secretion of cytokines by stromal cellsSecretedFactors - CYTOKINESBCell-cell contactStromal cellBone marrow stromal cells nurture developing B cellsTypes of cytokines and cell-cell contacts needed at each stage of differentiation are differentMaturing B cellsBone marrow stromal cellBBStromal cellB lineage commitmentHSCHSC (hematopoietic stem cell)MPP (淋巴系髓系多能前体细胞) ELP (earliest lymphocyte progenitor)ETP (early T-lineage progenitor)CLP (common lymphoid progenitor) Development and migration of B cells (An overview)Pre-B cellreceptorexpressedStages of differentiation in the bone marrow aredefined by Ig gene rearrangementB CELL STAGEIgH GENECONFIGURATIONStem cellEarly pro-BLate pro-BLarge pre-BGermlineDH to JHVH to DHJHVHDHJHIg light chain gene has not yet rearrangedHeavy chainVHDHJHLight chainVLJLCLVpreBl5CHmIga Igb signaltransductionmoleculesPre-B cell receptor
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