The MHC Class II Cofactor HLA-DM Interacts with Ig in B Cells

B cells internalize extracellular Ag into endosomes using the Ig component of the BCR. In endosomes, Ag-derived peptides are loaded onto MHC class II proteins. How these pathways intersect remains unclear. We find that HLA-DM (DM), a catalyst for MHC class II peptide loading, coprecipitates with Ig in lysates from human tonsillar B cells and B cell lines. The molecules in the Ig/DM complexes have mature glycans, and the complexes colocalize with endosomal markers in intact cells. A larger fraction of Ig precipitates with DM after BCR crosslinking, implying that complexes can form when DM meets endocytosed Ig. In vitro, in the endosomal pH range, soluble DM directly binds the Ig Fab domain and increases levels of free Ag released from immune complexes. Taken together, these results argue that DM and Ig intersect in the endocytic pathway of B cells with potential functional consequences.