Document Type

Honors Project On-Campus Access Only

Abstract

Thymic B cells are a subpopulation of B lymphocytes that reside in the thymic medulla, an organ that is specialized for the development and selection of T lymphocytes. Thymic B cells are activated by CD40L+ CD4 single positive thymocytes, leading to the upregulation of MHC-II, costimulatory molecules CD80 and CD86, initiation of immunoglobulin class switch recombination (CSR), resulting in the licensing of thymic B cells as professional antigen-presenting cells (APCs). The thymus also harbors other APC populations such as dendritic cells and medullary thymic epithelial cells (mTECs) that use unique strategies of self-antigen expression and presentation to mediate central tolerance. Whether thymic B cells confer unique tolerogenic features on developing thymocytes is not fully understood. From T cell receptor (TCR) repertoire deep sequencing, we identified CD4 single positive thymocytes that were dependent on licensed thymic B cells for development. Furthermore, testing these TCRs using intrathymic transfers and hybridoma cell lines demonstrated licensed B cells may be critical for the optimal development of a substantial fraction of the Foxp3 regulatory T (Treg) cell repertoire and likely play an essential tolerogenic role in the generation of a healthy Treg cell repertoire.

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