SELIL and HRD1 are involved in the degradation of unassembled secretory Ig-μ chains

When expressed in the absence of light chains, secretory I1g-mu chains (R,) undergo endoplasmic reticulum associated degradation (ERAD). This process involves the recognition of terminally misfolded or unassembled molecules, their retro-translocation across the ER membrane and ubiquitination for degradation by cytosolic proteasomes. The molecular components of the ERAD pathway and their coordination remain largely unknown. Here we employed co-immunoprecipitation, silencing or over-expression assays to show that SELIL and HRD1 are involved in the degradation of unassembled Ig-mu(s), but have minor effects on another substrate, TCR-alpha. SELIL and HRD1 localize in the early secretory apparatus and are induced by ER stress and during B cell differentiation, concomitantly with the onset of massive IgM secretion. These findings reveal a role for SELIL and HRD1 in IgM quality control.