Human germinal center B cells are intrinsically able to discriminate antigen affinity and with T cell help express plasma cell transcription factors

Abstract

Abstract The selection of GC B cells that express high affinity B cell receptors (BCRs) is driven by the ability of B cells to both signal through the BCR and to extract antigen and present it to follicular helper T cells (T FH cells). Using anti-kappa antibodies of low (KD=3.9×10 −7 ) versus high (KD=2.4×10 −9 ) affinities attached to membranes as surrogate antigens, we show that LZ GC B cells are able to discriminate between these and responded only to the high affinity antigen. In contrast, naïve B cells responded to both high and low affinity antigens. LZ GC B cells engaged membrane associated surrogate antigens through highly dynamic F-actin and ezrin-rich pod-like structures that concentrated BCRs at their contact points. Using DNA-based mechanical force nano-sensors we observed robust pulling forces localized to the contact sites of the pods with the membrane. In contrast, naïve B cells formed flat stable contacts with the membranes and showed only defuse weak pulling forces. GC B cells optimally express transcription factors that drive plasma cell differentiation, namely IRF-4 and PRDM-1, in response to antigen in combination with T FH help while naïve B cells increased IRF-4 and PRDM-1 transcription in response to T FH alone and less so to antigen alone. Thus, LZ GC B cells appear to be intrinsically capable of antigen affinity discrimination and with the acquisition of T FH help BCR-activated LZ GC B cells differentiate into plasma cells.