Coalescence of B cell receptor and invariant chain MHC II in a raft-like membrane domain.

The BCR binds antigen for processing and subsequent presentation on MHC II molecules. Polyvalent antigen induces BCR clustering and targeting to endocytic processing compartments, which are also accessed by Ii-MHC II. Here, we report that clustered BCR is able to team up with Ii-MHC II already at the plasma membrane of mouse B-lymphocytes. Colocalization of BCR and Ii-MHC II on the cell surface required clustering of both types of molecules. The clustering of only one type did not trigger the recruitment of the other. Ii-bound MIF (a ligand of Ii) also colocalized with clustered BCR upon oligomerization of MIF on the surface of the B cell. Abundant surface molecules, such as B220 or TfnR, did not cocluster with the BCR. Some membrane raft-associated molecules, such as peptide-loaded MHC II, coclustered with the BCR, whereas others, such as GM1, did not. The formation of a BCR- and Ii-MHC II-containing membrane domain by antibody-mediated clustering was independent of F-actin and led to the coendocytosis of its constituents. With a rapid Brij 98 extraction method, it was possible to capture this membrane domain biochemically as a DRM. Ii and clustered BCR were present on the same DRM, as shown by immunoisolation. The coalescence of BCR and Ii-MHC II increased tyrosine phosphorylation, indicative of enhanced BCR signaling. Our work suggests a novel role for MIF and Ii-MHC II in BCR-mediated antigen processing.