Type III interferon enhances thymic B cell licensing

Abstract

Abstract The activation of thymic B cells is critical for their licensing as antigen presenting cells and resulting ability to mediate central immune tolerance. The processes leading to thymic B cell licensing are still not fully understood. By comparing thymic B cells to activated Peyer’s Patch B cells at steady state, we found that thymic B cell activation starts during the neonatal period and is characterized by immunoglobulin class switch recombination (CSR) without germinal center B cell phenotypes or structures. Transcriptional profiling supported the finding of extrafollicular activation of thymic B cells, but also demonstrated a strong interferon signature distinct from peripheral B cell activation. Removal of type I, II and III IFN receptors revealed thymic B cell activation and CSR were partially dependent on type III IFN signaling, while type I and II IFN signaling showed minimal contribution. Loss of type III IFN signaling in thymic B cells resulted in reduced licensing and alterations in self-antigen presentation. Together, these findings reveal the importance of type III IFN in generating tolerogenic thymic B cells and suggests inflammation in the thymus has a significant impact on the generation of central immune tolerance to B cell self-antigens.