Cutting edge: signals from the B lymphocyte antigen receptor regulate MHC class II containing late endosomes.
The B lymphocyte response to protein Ag is dependent upon the successful presentation to T cells of Ag-derived, MHC class II-restricted peptides. The B cell Ag receptor (BCR) facilitates this process by internalizing ligand and delivering it to specialized compartment(s) (MHC class II peptide-loading compartments (MIIC)) where it is processed into peptides and loaded onto MHC class II. In addition to efficiently targeting Ag, the BCR can provide tyrosine kinase-dependent signals that augment the presentation of Ag, possibly by enhancing the generation of immunogenic peptides. However, the mechanism by which this occurs is unclear. Herein, we report that the BCR signals a reorganization, fusion, and acidification of an MHC-like compartment into an invariant chain- and MHC class II-rich complex of large vesicles. This complex becomes the primary target for endocytosed receptors. These data suggest that signals generated by the BCR regulate the site of Ag processing.
Siemasko
K
K
Department of Medicine, Committee on Immunology, University of Chicago, IL 60637, USA.
Eisfelder
B J
BJ
Williamson
E
E
Kabak
S
S
Clark
M R
MR
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D011992:Endosomes / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D013347:Subcellular Fractions / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D000949:Histocompatibility Antigens Class II; D051907:Lysosomal Membrane Proteins; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell