Clonal Evolution of Autoreactive Germinal Centers.
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.
Duke Scholars
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Related Subject Headings
- Mice, Inbred C57BL
- Mice
- Kidney
- Immune Tolerance
- Germinal Center
- Epitopes
- Developmental Biology
- Clonal Evolution
- Chimera
- B-Lymphocytes
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Mice, Inbred C57BL
- Mice
- Kidney
- Immune Tolerance
- Germinal Center
- Epitopes
- Developmental Biology
- Clonal Evolution
- Chimera
- B-Lymphocytes