Thymus antibody-secreting cells possess an interferon gene signature and are preferentially expanded in young female mice

Summary: Antibody-secreting cells (ASCs) are key contributors to humoral immunity through immunoglobulin production and the potential to be long-lived. ASC persistence has been recognized in the autoimmune thymus (THY); however, only recently has this population been appreciated in healthy THY tissue. We showed that the young female THY was skewed toward higher production of ASCs relative to males. However, these differences disappeared with age. In both sexes, THY ASCs included Ki-67+ plasmablasts which required CD154(CD40L) signals for their propagation. Single cell RNA-sequencing revealed that THY ASCs were enriched for an interferon responsive transcriptional signature relative to those from bone marrow and spleen. Flow cytometry confirmed that THY ASCs had increased levels of Toll-like receptor 7 as well as CD69 and major histocompatibility complex class II. Overall, we identified fundamental aspects of THY ASC biology which may be leveraged for future in depth studies of this population in both health and disease.