Clonal Evolution of Autoreactive Germinal Centers.

Published

Journal Article

Germinal centers (GCs) are the primary sites of clonal B cell expansion and affinity maturation, directing the production of high-affinity antibodies. This response is a central driver of pathogenesis in autoimmune diseases, such as systemic lupus erythematosus (SLE), but the natural history of autoreactive GCs remains unclear. Here, we present a novel mouse model where the presence of a single autoreactive B cell clone drives the TLR7-dependent activation, expansion, and differentiation of other autoreactive B cells in spontaneous GCs. Once tolerance was broken for one self-antigen, autoreactive GCs generated B cells targeting other self-antigens. GCs became independent of the initial clone and evolved toward dominance of individual clonal lineages, indicating affinity maturation. This process produced serum autoantibodies to a breadth of self-antigens, leading to antibody deposition in the kidneys. Our data provide insight into the maturation of the self-reactive B cell response, contextualizing the epitope spreading observed in autoimmune disease.

Full Text

Duke Authors

Cited Authors

  • Degn, SE; van der Poel, CE; Firl, DJ; Ayoglu, B; Al Qureshah, FA; Bajic, G; Mesin, L; Reynaud, C-A; Weill, J-C; Utz, PJ; Victora, GD; Carroll, MC

Published Date

  • August 2017

Published In

Volume / Issue

  • 170 / 5

Start / End Page

  • 913 - 926.e19

PubMed ID

  • 28841417

Pubmed Central ID

  • 28841417

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2017.07.026

Language

  • eng