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

Autor:	van der Poel CE; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Bajic G; Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Macaulay CW; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Boston University, Boston, MA 02215, USA., van den Broek T; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Ellson CD; GSK, Stevenage, Hertfordshire, SG1 2NY, UK., Bouma G; GSK, Stevenage, Hertfordshire, SG1 2NY, UK., Victora GD; The Rockefeller University, New York, NY 10065, USA., Degn SE; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Carroll MC; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: michael.carroll@childrens.harvard.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2019 Nov 26; Vol. 29 (9), pp. 2745-2755.e4.
DOI:	10.1016/j.celrep.2019.10.086
Abstrakt:	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 AidCre ERT2 -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. (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu