Self-Antigen-Driven Thymic B Cell Class Switching Promotes T Cell Central Tolerance

Cell Rep. 2016 Oct 4;17(2):387-398. doi: 10.1016/j.celrep.2016.09.011.


B cells are unique antigen-presenting cells because their antigen presentation machinery is closely tied to the B cell receptor. Autoreactive thymic B cells can efficiently present cognate self-antigens to mediate CD4+ T cell-negative selection. However, the nature of thymocyte-thymic B cell interaction and how this interaction affects the selection of thymic B cell repertoire and, in turn, the T cell repertoire are not well understood. Here we demonstrate that a large percentage of thymic B cells have undergone class switching intrathymically. Thymic B cell class switching requires cognate interaction with specific T cells. Class-switched thymic B cells have a distinct repertoire compared with unswitched thymic B cells or splenic B cells. Particularly, autoreactive B cell specificities preferentially expand in the thymus by undergoing class switching, and these enriched, class-switched autoreactive thymic B cells play an important role in CD4 T cell tolerance.

Keywords: B cell class switching; T cell negative selection; antigen presentation; autoreactive B cell; autoreactive T cell; self-antigen; thymic B cells; tolerance.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism
  • Autoantigens / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • Central Tolerance / immunology*
  • Humans
  • Immunoglobulin Class Switching / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • T-Lymphocytes / immunology*
  • Thymocytes / immunology
  • Thymocytes / metabolism


  • Autoantigens