Follicular Dendritic Cells Modulate Germinal Center B Cell Diversity through FcγRIIB

Abstract

Summary: Follicular dendritic cells (FDCs), a rare and enigmatic stromal cell type in the B cell follicles of secondary lymphoid organs, store and present antigen to B cells. While essential for germinal center (GC) responses, their exact role during GC B cell selection remains unknown. FDCs upregulate the inhibitory IgG Fc receptor FcγRIIB during GC formation. We show that the stromal deficiency of FcγRIIB does not affect GC B cell frequencies compared to wild-type mice. However, in the absence of FcγRIIB on FDCs, GCs show aberrant B cell selection during autoreactive and selective foreign antigen responses. These GCs are more diverse as measured by the AidCreERT2 -confetti system and show the persistence of IgM+ clones with decreased numbers of IgH mutations. Our results show that FDCs can modulate GC B cell diversity by the upregulation of FcγRIIB. Permissive clonal selection and subsequent increased GC diversity may affect epitope spreading during autoimmunity and foreign responses. : van der Poel et al. show that follicular dendritic cells (FDCs) can regulate germinal center diversity through FcγRIIB. In the absence of this receptor, germinal centers appear more diverse. In addition, the loss of FcγRIIB on FDCs leads to the persistence of IgM clones with decreased levels of somatic hypermutation. Keywords: follicular dendritic cells, FcγRIIB, CD32, germinal center, clonal selection, autoimmunity