Scavenger receptor CD36 on B cells senses modified self-antigens to prevent autoimmunity

Scavenger receptor CD36 has been shown to mediate uptake of modified self-antigens such as apoptotic cells and oxidized LDL in macrophages and dendritic cells. Interestingly, CD36 was discovered to be preferentially expressed also on an innate B cell subtype, marginal zone B cells (MZB). Here we investigate the role of CD36 in B cell activation in the context of apoptotic cell clearance and break of tolerance to self. We found that formation of germinal center B cells and autoantibody production in response to an increased load of apoptotic cells coincide with downregulation of CD36 on MZB. We could also in connection to this show that systemic lupus erythematosus (SLE) patients have lower levels of peripheral MZB compared to healthy individuals. B cells lacking CD36 proved more easily activated in response to apoptotic cells, as was shown in bone marrow (BM) chimeras reconstituted with wild type and CD36-deficient BM. In steady-state, we found that CD36 co-localizes with the B cell receptor and the tyrosine kinase Lyn. Interestingly, upon cross-linking of the inhibitory Fc receptor, FcgRIIb, CD36 instead co-localizes with this receptor. This suggests that CD36 interacts with FcgRIIb to activate a negative signaling cascade in B cells. Our data implicate CD36 in the early regulation of B cell responses towards apoptotic cells and autoantibody production. In line with this we find that CD36-deficient B cells are more resistant to FcgRIIb-induced cell death. Thus, CD36 exerts its regulatory function by associating with a known negative signaling pathway in B cells involving Lyn and FcgRIIb. This finding could have implications for autoimmune diseases involving apoptotic cell-derived self-antigens, such as SLE.