Antibody-dependent priming of spontaneous germinal centers by autoreactive B cells

Authors

Kim, D., Chiang, K., Largent, A. D., Pitner, R. A., Ponnan, S. M., McKinney, B. J., James, R. G., Rawlings, D. J., Jackson, S. W.

Abstract

Autoreactive germinal centers (GCs) are central to autoimmune pathogenesis, yet the mechanisms by which single autoreactive B cell clones prime systemic autoimmunity remain unclear. Using the 564Igi mixed chimera model, we demonstrate that autoreactive 564Igi B cells break tolerance in wild-type B cells through an unexpected mechanism independent of cognate T cell interactions. While B cell-intrinsic TLR7 signaling was essential for spontaneous GC formation, deletion of MHC class II, CD40, or CD80/86 on GC-priming 564Igi B cells failed to prevent GCs. Instead, CRISPR-mediated deletion of Prdm1 (encoding BLIMP-1) in 564Igi B cells ablated spontaneous GCs, implicating autoantibody production as the primary driver. These findings reveal that autoantibodies can initiate feed-forward mechanisms that propagate systemic autoimmunity, independent of B cell-intrinsic antigen presentation.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 03 Sep 2026.

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