Identifying the microenvironmental requirements of thymic B cell licensing 4727

Abstract Description Thymocyte development and resulting central tolerance occur in a step wise fashion that is dependent on T cell receptor (TCR) recognition of self-peptides presented by thymic antigen presenting cells (APCs). Thymic epithelial cells and APCs are maintained in unique microenvironments within the thymus, and their structural organization likely plays a role in T cell central tolerance. B cells, an important APC population in the thymus, require TCR:pMHCII interaction, CD40-CD40L signaling and type-III IFN to become licensed and select for Foxp3+ regulatory T (Treg) cells. However, how and where the B cells interact with thymocytes and epithelial cells to receive these signals is unknown. Using multiplex iterative imaging, we have identified distinct microenvironments of naïve and isotype class-switched B cells, as well as plasmacytoid dendritic cells (pDCs) and conventional dendritic cells within the thymic medulla. We find that isotype class-switched B cells are in proximity with GP2-expressing medullary thymic epithelial cells (mTECs), and that these clusters are adjacent to type-III IFN producing mTEC. Future studies will test the requirements for establishing thymic B cell microenvironments and determine how alterations to these interactions impact T cell central tolerance. Funding Sources K99AI184587 Topic Categories Hematopoiesis and Immune System Development (HEM)