title: MHC class II antigen processing in B cells: accelerated intracellular targeting of antigens.
abstract: Processing and presentation by Ag-specific B cells is initiated by Ag binding to the B cell Ag receptor (BCR). Cross-linking of the BCR by Ag results in a rapid targeting of the BCR and bound Ag to the MHC class II peptide loading compartment (IIPLC). This accelerated delivery of Ag may be essential in vivo during periods of rapid Ag-driven B cell expansion and T cell-dependent selection. Here, we use both immunoelectron microscopy and a nondisruptive protein chemical polymerization method to define the intracellular pathway of the targeting of Ags by the BCR. We show that following cross-linking, the BCR is rapidly transported through transferrin receptor-containing early endosomes to a LAMP-1+, beta-hexosaminadase+, multivesicular compartment that is an active site of peptide-class II complex assembly, containing both class II-invariant chain complexes in the process of invariant chain proteolytic removal as well as mature peptide-class II complexes. The BCR enters the class II-containing compartment as an intact mIg/Igalpha/Igbeta complex bound to Ag. The pathway by which the BCR targets Ag to the IIPLC appears not to be identical to that by which Ags taken up by fluid phase pinocytosis traffick, suggesting that the accelerated BCR pathway may be specialized and potentially independently regulated.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Cheng
authors.forename: C R
authors.initials: CR
authors.lastname: Steele
authors.forename: L
authors.initials: L
authors.lastname: Gu
authors.forename: W
authors.initials: W
authors.lastname: Song
authors.forename: S K
authors.initials: SK
authors.lastname: Pierce
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D001665:Binding Sites / Q000276:immunology; D002384:Catalysis; D002451:Cell Compartmentation / Q000276:immunology; D004705:Endocytosis / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D006735:Horseradish Peroxidase / Q000276:immunology / Q000378:metabolism; D007106:Immune Sera / Q000494:pharmacology; D007424:Intracellular Fluid / Q000276:immunology* / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D016253:Microscopy, Immunoelectron; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D010873:Pinocytosis / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D011990:Receptors, Transferrin / Q000378:metabolism; D013347:Subcellular Fractions / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D007106:Immune Sera; D007976:Leupeptins; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D010455:Peptides; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D011990:Receptors, Transferrin; C045084:invariant chain; D006735:Horseradish Peroxidase; D001619:beta-N-Acetylhexosaminidases; C032854:leupeptin