ATG5 controls CD80 expression in B cells and shapes cognate CD4+ T cell responses.

Abstract

The macroautophagy/autophagy machinery has been implicated in supporting MHC class II but compromising MHC class I restricted antigen presentation by dendritic cells (DCs). Here, we report that loss of the essential autophagy protein ATG5 in B cells reduces internalization and stabilizes co-stimulatory CD80 surface expression. In an adjuvant-free experimental autoimmune encephalomyelitis (EAE) mouse model, co-transfer of MOG-specific induced germinal center B (iGB) cells deficient in ATG5 with MOG-specific CD4⁺ T cells, accelerated disease development. CD80 blockade abrogated enhanced cognate CD4⁺ T-cell responses induced by iGB cells lacking ATG5. These data broaden the concept of ATG5-mediated antigen presentation and indicate that ATG5 might not only enhance, as described previously with MHC class II-restricted presentation in DCs, but also limit the activation of CD4⁺ T cells through attenuating CD80 expression on B cells.Abbreviations: APC: antigen-presenting cell; CNS: central nervous system; DC: dendritic cell; EAE: experimental autoimmune encephalomyelitis; iGB: induced germinal center B cell; MOG: myelin oligodendrocyte glycoprotein; MS: multiple sclerosis.