Loss of BECN1 does not compromise autophagosome formation but alters cargo selection and HLA-restricted antigen presentation of B cells.

BECN1 (beclin 1) is a member of the nucleation complex and considered crucial for induction of macroautophagy/autophagy, leading to the formation and ultimate degradation of autophagosomes. We found that in human B lymphoblastoid cell lines (LCLs) deficient of BECN1 (BECN1-KO), autophagosome formation was intact and autophagic flux could be induced upon nutrient starvation or MTOR inhibition. Remarkably, autophagosomal cargo differed significantly between BECN1-KO and control (CTRL) LCLs, revealing a preferred formation of autophagosomes at the endoplasmic reticulum (ER) and not at endosomes/lysosomes in BECN1-KO LCLs. Endosomal TLR3 (toll like receptor 3) was less frequently incorporated within autophagosomes in BECN1-KO LCLs. Additionally, several proteins of the ER-resident peptide loading complex for MHC class I antigen presentation were found enriched in autophagosomes from BECN1-KO LCLs, resulting in a diminished detection of BECN1-KO LCLs by T cells. Hence, BECN1 seems to be dispensable for autophagosome formation but rather contributes to cargo selection of phagophores and immunosurveillance.Abbreviations: ATG: autophagy-related; BECN1: beclin 1; CTRL: control; LCL: Epstein Barr virus transformed lymphoblastoid cell line; MHC: major histocompatibility complex; PLC: peptide-loading complex; TLR: toll like receptor.