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

Abstract

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.