The outcome of B cell differentiation is regulated by the induction and activation of different transcription factors. It is clear from the discussion so far that activated B cells can follow several fates. They can develop into short-lived or long-lived plasma cells, which secrete large amounts of antibodies, or into long-lived memory cells, which do not secrete antibodies but survive for prolonged periods and respond rapidly to antigen challenge. In Chapter 9, we discussed the concept that T cell fates are determined in large part by the expression of various transcriptional activators and repressors. The same general principle applies to the fates of activated B cells.
In germinal center B cells, signals delivered through CD40 and the IL-21 receptor induce the expression of a transcriptional repressor called Bcl-6. Bcl-6 antagonizes another repressor called Blimp-1, which is required for plasma cell development (see later) and thus prevents cells in the germinal center from differentiating into plasma cells during the massive proliferation that is characteristic of the germinal center reaction. B cells in extra-follicular foci express lower levels of Bcl-6 and more readily develop into short-lived plasma cells. Bcl-6 and other transcriptional regulators help orchestrate rapid
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