Antigen-specific transendocytosis of CD40 ligand accompanies T cell help for B cells

Abstract It has been known for decades that the delivery of T cell help to B cells is antigen-specific, MHC-restricted, and depends on CD40L. However the mechanisms by which CD40L, a transmembrane cytokine, is delivered to the T cell surface and engages CD40 on antigen-presenting B cells remains to be determined. 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. We show for the first time 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. Transfer of CD40L is nearly absent from bystander B cells that are not presenting antigen. It was recently discovered that peptide-MHC engaged TCRs are deposited on B cells in microvesicles at the immunological synapse. Our data suggest that CD40L might be deposited in a similar manner as a secreted vesicle. CD40-engaged CD40L on vesicles could allow for sustained signaling in antigen-presenting B cells despite the brief interactions with helper T cells that occur in vivo in germinal centers.