Antigen presentation by B cells enables epitope spreading across an MHC barrier

Nat Commun. 2023 Oct 31;14(1):6941. doi: 10.1038/s41467-023-42541-7.


Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. Here, to test this hypothesis, we used a murine model in which a single B cell clone precipitates an autoreactive response resembling systemic lupus erythematosus (SLE). The initiating clone did not need to enter germinal centers to precipitate epitope spreading. Rather, it localized to extrafollicular splenic bridging channels early in the response. Autoantibody produced by the initiating clone was not sufficient to drive the autoreactive response. Subsequent epitope spreading depended on antigen presentation and was compartmentalized by major histocompatibility complex (MHC). B cells carrying two MHC haplotypes could bridge the MHC barrier between B cells that did not share MHC. Thus, B cells directly relay autoreactivity between two separate compartments of MHC-restricted T cells, leading to inclusion of distinct B cell populations in germinal centers. Our findings demonstrate that B cells initiate and propagate the autoimmune response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation*
  • B-Lymphocytes
  • Epitopes
  • Histocompatibility Antigens
  • Histocompatibility Antigens Class II / genetics
  • Lupus Erythematosus, Systemic*
  • Major Histocompatibility Complex
  • Mice


  • Epitopes
  • Histocompatibility Antigens Class II
  • Histocompatibility Antigens