Past Antigen Exposures are Epigenetically Imprinted and Determine the Memory B Cell Fate Upon Rechallenge
SHAO Wen1,2,3,4, QI Hai1,2,3,4*
Memory B cells are crucial components of long-term humoral immunity. Upon antigen re exposure, memory B cells can rapidly become antibody-producing plasma cells or they can re-enter GCs (germinal centers) to undergo further antibody somatic hypermutation and affinity maturation. Memory B cell re-participation in the GC reaction is thought to be important for generating broadly neutralizing antibodies against highly mutating viruses such as influenza virus and HIV. The fate of memory B cells into plasma cells or GC B cells following an tigen re-stimulation is associated with distinct antibody isotypes and memory B cell surface phenotypes. However, whether these memory B cell fates are intrinsically programmed by transcriptional and epigenetic mechanisms was not understood. This study finds that each stimulation experienced by memory B cells is epigenetically recorded in an IRF4-dependent manner, which determines the relative levels of two antagonistic transcription factors BLIMP1 and BACH2 in B cells, and in turn dictates the likelihood that a memory B cell enters a germinal center or becomes a plasma cell upon re-stimulation.
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