title: Coalescence of B cell receptor and invariant chain MHC II in a raft-like membrane domain.
abstract: 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.
authors.affiliation: Hannover Medical School, Department of Cell Biology, Center for Anatomy, Hannover, Germany.
authors.forename: Julian T
authors.initials: JT
authors.lastname: Hauser
authors.affiliation: Hannover Medical School, Department of Cell Biology, Center for Anatomy, Hannover, Germany lindner.robert@mh-hannover.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Lindner
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D004705:Endocytosis / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D055503:Protein Multimerization; D021381:Protein Transport; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000199:Actins; D000941:Antigens; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D011947:Receptors, Antigen, B-Cell; C045084:invariant chain
keywords: B-lymphocyte; BCR; CD74; MIF; antigen presentation; lipid raft