Antigen-specific transfer of CD40L to antigen-presenting B cells during T cell help

Abstract

It has been known for decades that the delivery of T cell help to B cells is antigen-specific, MHC-restricted, and depends CD40L (CD154). It has been thought that when a T cell recognizes an antigen-presenting B cell, CD40L expressed on the T cell surface engages with CD40 on the surface of B cells as long as the cells remain conjugated. Addition of fluorescently labeled anti-CD40L antibody during overnight incubation of antigen-presenting B cells with antigen-specific T cells allowed us to discover that CD40L does not remain on the surface of the T cell, but is transferred to and endocytosed by B cells receiving T cell help. In the presence of anti-CD40L antibody, transferred CD40L is nearly absent on bystander B cells that are not presenting antigen, and the bystander cells do not become activated. Because transfer of CD40L to B cells correlates with B cell activation, we speculate that persistence of helper T cell-derived CD40L on or in B cells could permit sustained CD40 signaling enabling survival and proliferation of antigen-presenting B cells following brief interactions with helper T cells in vivo in germinal centers.