Regulation of B cell function and expression of CD11c, T-bet, and FcRL5 after infection and in response to different activation pathways

CD11c, FcRL5, or T-bet are commonly expressed by B cells expanding during inflammation, where they can make up >30% of mature B cells. However, the association between the proteins and differentiation and function in the host response remain largely unclear. We have assessed the co-expression of CD11c, T-bet and FcRL5 over one year in patients treated for malaria. We observed dynamic co-expression profiles that changed over time, suggesting ongoing differentiation. We used an in vitro B cell culture system to determine how stimulation via the B cell receptor (BCR), toll-like receptor 9 (TLR9), and different cytokines could influence CD11c, T-bet, and FcRL5 expression. We observed different expression dynamics for all markers, but a largely overlapping regulation of CD11c and FcRL5 in response to BCR and TLR9 activation, while T-bet was strongly dependent on IFN-γ signalling. Investigating plasma cell differentiation and antigen-presenting cell functions, there was no association between marker expression and antibody secretion or T cell help, although the functions were associated with TLR9-signalling and B cell-derived IL-6 production, respectively. These results point to CD11c, FcRL5, and T-bet expression representing different activation stages and highlight the value of using multiple markers when assessing B cell differentiation. ### Competing Interest Statement The authors have declared no competing interest.