Cognate CD40-CD40L interaction maintains thymic B cells in absence of TCR-MHC interaction between thymic T and B cells

Abstract

Abstract We previously demonstrated that maintenance of the thymic B cell population requires cross-talk between thymic B cells and T cells, analogous to the cross-talk that had been demonstrated between thymic epithelial cells and developing T cells. Maintenance of thymic B cells specifically requires interaction between CD40 ligand (CD40L) and cell autonomous CD40 on thymic B cells. Co-stimulatory interactions such as those mediated by CD40 commonly exert their effects in concert with pMHC-specific T cell receptor (TCR) recognition. We have therefore analyzed the requirement for MHC-TCR interaction for thymic B cell maintenance. Analysis of mixed bone marrow (BM) chimeras constructed from MHCI/MHCII double knockout (DKO) and WT donor BM revealed that there is no requirement for expression of MHCI or MHCII on thymic B cells for their maintenance. Thus, the thymic B cell population is regulated by cognate CD40-CD40L interaction in the absence of direct pMHC-TCR interaction with T cells. Experiments are currently in progress to determine whether CD40-dependent thymic B cells are sustained by direct interaction with T cells expressing membrane-bound CD40L, or by soluble CD40L in the absence of direct T cell-B cell interaction.