Follicular Dendritic Cells Modulate Germinal Center B Cell Diversity through FcγRIIB

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Dendritic Cells, Follicular / immunology*
  • Germinal Center / immunology*
  • Humans
  • Mice
  • Receptors, IgG / genetics*

Substances

  • Receptors, IgG