Interferon dependent genes of intrathymic antigen presenting cells

The activation of thymic B cells is critical for their licensing as antigen presenting cells and resulting ability to mediate central tolerance. The processes leading to 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 TCR/CD40 dependent activation, followed by immunoglobulin class switch recombination (CSR) without forming germinal centers. Transcriptional analysis also demonstrated a strong interferon signature, which was not apparent in the periphery. Thymic B cell activation and CSR were primarily dependent on type III IFN signaling, and loss of type III IFN receptor in thymic B cells resulted in reduced thymocyte regulatory T cell (Treg) development. Finally, from TCR deep sequencing, we estimate that licensed B cells induce development of a substantial fraction of the Treg cell repertoire. Together, these findings reveal the importance of steady state type III IFN in generating licensed thymic B cells that generate T cell tolerance to activated B cells MHC-II-expressing cells sorted from the thymus of 5-week-old wildtype (WT), Ifnar1-/- (IFNAR-KO) and Ifnar1-/-/Ifnlr1-/- (IFNAR/IFNLR-DRKO) mice were submitted for scRNA sequencing.