B-CELLS…Origin…Development…SelectionS.pptVIP

B-CELLS… Origin… Development… SelectionS ActivationS NEGATIVE selection: crosslinkage of mIgM on immature B cells can cause cells to die within the bone marrow aka: CLONAL DELETION Nota bene: Prior to clonal deletion, development is antigen independent. Negative selection and positive selection are antigen dependent. Recognition of the ANTIGEN in the periphery leads to positive selection… aka CLONAL EXPANSION SELECTION does not equal ACTIVATION… Recall that a B-CELL needs a signal from a T-HELPER CELL SELECTION does not equal ACTIVATION… Recall that a B-CELL needs a signal from a T-HELPER CELL SELECTION does not equal ACTIVATION… Recall that a B-CELL needs a signal from a T-HELPER CELL Activation…. Activation occurs when a B-cell associates with a T-helper cell through a ternary complex; this association establishes specificity (the B-cell will have processed the antigen and presented it through MHC-II, thus selecting a specific T-helper cell lineage). Pairing between B7 on the B-cell and CD28 on the T-helper cell constitutes a co-stimulatory signal which will activate the T-helper cell. (The identities of the co-stimulatory proteins are “specific”; but these same proteins are involved regardless of the identity of the antigen). The T-helper cell , once activated, synthesizes CD40L. Now, pairing occurs between CD40 on the B-cell and CD40L on the T-helper cell . This association constitutes a co-stimulatory signal which activates the B-cell. Thus, there is “mutuality” between the B-cell activating the T-helper cell and the activated T-helper cell, in turn, activating the B-cell. (This “mutuality” should not obscure that the process is “antigen-driven.”) Cytokines of various types are secreted by T-helper cell and are received by differentiating B-cells. The various cytokines affect what immunoglobulin isotypes will be produced by plasma cells. Where is activation happening?And what is happening? The primary response is initiated i