Follicular Dendritic Cells Modulate Germinal Center B Cell Diversity through FcγRIIB

滤泡树突状细胞通过FcγRIIB调节生发中心B细胞多样性

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作者:Cees E van der Poel ,Goran Bajic ,Charles W Macaulay ,Theo van den Broek ,Christian D Ellson ,Gerben Bouma ,Gabriel D Victora ,Søren E Degn ,Michael C Carroll

Abstract

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.

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