Histone chaperone CHAF1B facilitates germinal center B cell differentiation via cooperation with BCL6 and TBL1XR1.

BCL6 is a master regulator of germinal center (GC) B cells. Further identification and characterization of factors that may play a role within the BCL6 network is important for our understanding of GC B cell differentiation and function. Here, through co-Immunoprecipitation coupled with mass spectrometry, we identify CHAF1B as a new partner in the BCL6 complex, which is highly expressed in GC B cells, promoting GC formation and humoral immunity. Loss of CHAF1B impairs the dark zone (DZ) and light zone (LZ) organization and induces apoptosis, resulting in abnormal GC responses and antibody production. Mechanistically, CHAF1B stabilizes BCL6/TBL1XR1 complex to promote GC B cell differentiation by cooperative transcriptional repression. Furthermore, overexpression of CHAF1B in B cells reduces the plasmablast by extending GC reaction, which is positively related to the production of high affinity antibodies in response to vaccines or pathogens. These findings not only advance the understanding of GC biology but also had potential implications for developing targeted strategies to improve vaccination efficacy.