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

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.

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BibTeX RIS

BibTeX

@misc{kim2026antibodydependent,
  title = {{Antibody-dependent priming of spontaneous germinal centers by autoreactive B cells}},
  author = {D. Kim and K. Chiang and A. D. Largent and R. A. Pitner and S. M. Ponnan and B. J. McKinney and R. G. James and D. J. Rawlings and S. W. Jackson},
  howpublished = {bioRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.27.745373},
  url = {https://www.biorxiv.org/content/10.64898/2026.08.27.745373v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Antibody-dependent priming of spontaneous germinal centers by autoreactive B cells
AU  - D. Kim
AU  - K. Chiang
AU  - A. D. Largent
AU  - R. A. Pitner
AU  - S. M. Ponnan
AU  - B. J. McKinney
AU  - R. G. James
AU  - D. J. Rawlings
AU  - S. W. Jackson
PY  - 2026
DA  - 2026/08/27
PB  - bioRxiv
DO  - 10.64898/2026.08.27.745373
UR  - https://www.biorxiv.org/content/10.64898/2026.08.27.745373v1
AB  - 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.
ER  -

Abstract

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