Autophagy connects antigen receptor signaling to costimulatory signaling in B lymphocytes.

In primary B lymphocytes (B cells), antigen stimulation induces transmembrane signaling through the B cell antigen receptor (BCR) that induces apoptosis. Activation of antigen-stimulated B cells requires additional signals termed costimulatory signals such as CD40L and TLR ligands that rescue B cells from apoptosis and induce their activation and proliferation. BCR signaling rapidly induces extensive autophagosome formation in B cells. Lines of evidence suggest that, in B cells as well as other cell types such as dendritic cells, autophagosomes play a role in efficient antigen presentation, a process in which antigenic peptides are expressed on the cell surface in a form complexed with major histocompatibility complex (MHC) molecules for recognition by T cells. Because antigen presentation of B cells is crucial for interaction with CD40L-expressing T helper cells, autophagy plays a role in connecting BCR signaling to costimulatory signaling through CD40. Recently, BCR ligation was demonstrated to translocate TLR9, a costimulatory receptor for pathogen-derived nucleic acids, to autophagosomes where TLR9 appears to interact with its ligands. Based on these findings we propose that autophagy plays a key role in connecting BCR signaling to costimulatory signaling.