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Cell Rep. 2019 Nov 26;29(9):2745-2755.e4. doi: 10.1016/j.celrep.2019.10.086.

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

Author information

1
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
2
Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
3
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Boston University, Boston, MA 02215, USA.
4
GSK, Stevenage, Hertfordshire, SG1 2NY, UK.
5
The Rockefeller University, New York, NY 10065, USA.
6
Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
7
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: michael.carroll@childrens.harvard.edu.

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.

KEYWORDS:

CD32; FcγRIIB; autoimmunity; clonal selection; follicular dendritic cells; germinal center

PMID:
31775042
DOI:
10.1016/j.celrep.2019.10.086
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