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Follicular Dendritic Cells Modulate Germinal Center B Cell Diversity through Fc?RIIB.


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 Fc?RIIB during GC formation. We show that the stromal deficiency of Fc?RIIB does not affect GC B cell frequencies compared to wild-type mice. However, in the absence of Fc?RIIB 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 Fc?RIIB. Permissive clonal selection and subsequent increased GC diversity may affect epitope spreading during autoimmunity and foreign responses.

SUBMITTER: van der Poel CE 

PROVIDER: S-EPMC7015177 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Follicular Dendritic Cells Modulate Germinal Center B Cell Diversity through FcγRIIB.

van der Poel Cees E CE   Bajic Goran G   Macaulay Charles W CW   van den Broek Theo T   Ellson Christian D CD   Bouma Gerben G   Victora Gabriel D GD   Degn Søren E SE   Carroll Michael C MC  

Cell reports 20191101 9


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 FcγRI  ...[more]

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