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05 RSS flank all genes undergoing process of rearrangementguided by 1223 base pair rule Mediated by the products of Rag ne and two Various stages of recombination machinery including generation of hairpin Generation hairpin ends coding endsArtemis and ligases that join the ends that need to be joined together B cells that start off by expressing IgM for instance to switch to secreting IgM etc Coexpression of IgM and IgD on B cell surfaceOnce B cells undergo rearrangement at heavy chain locus to get rearrange VDJ sequence same VDJ sequence used both for the membrane and secreted form of IgD for theIgM and IgD expresesd by single cell and also IgM switched isotype after isotype switchinguse of same VDJ sequence so B cell will maintain same specificty as go through maturation In all bone marrownot just right arm in first column B cells or lymphocytes with specificity for self eliminated early in development Rearrangement process cannot distinguish btw self and foreign antigens Receptors are generated random Raceptors will interact with self antigen in bone marrowothers wont Surface ig receptors that interact with self antigen recognize self in bone marrownegatively selected SO REMOVED FROM REPERTOIRE OF B CELLSexported from bone marrow to periphery Coexpression of IgM and IgD on B cells urfaceconsidered marker of mature B cell B cells float aroundif encounter antigenantigen is likely to be foreign antigen and this foreign antigen will bind to surface receptor on B cells and activation of B cellsaction of B cell can lead to two major fatesDifferentiate into plasma cellconsidered terminally differeniatedcranks out high levels of Ig secreted for rest of its lifeto generate serum antibody seen in antibody responsesAlternatively as memory cellshave extended life spanrecirculate in bodycan react rapidly when there is second exposure to antigen Secondary antibody reponses more rapid than primary responesWHYPlasma and memory cells Plasma found in LN spleensome go back to bone marrow Memory cells continue to recirculate through secondary lymphoid organs and through blood stream B committment occurs in context of hematopoiesis HSC can differentiate into multipotent progenitor that can differentiate Ig genes only undego rearrangement in B cells not in T cells not in other cellscommitment to B cell lingeage must occur prior to rearrangemetn of Ig genes Commitment induced by bone marrow microenvironment Genes that cell expresseswhat makes cells different
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