B cell antigen receptor signaling links biochemical changes in the class II peptide-loading compartment to enhanced processing.
In B cells, processing of antigens in the context of MHC class II molecules is initiated by the binding of antigen to the B cell antigen receptor (BCR). BCR-mediated processing is highly efficient, as a consequence of the BCR's linked roles of delivering antigen to the class II peptide-loading compartment and of signaling for increased antigen-processing activity. Evidence is emerging that receptor signaling regulates intracellular transport through the activities of kinases. These in turn have been implicated in the regulation of small mol. wt GTPases which govern membrane transport. Therefore, we investigated the changes in the phosphoprotein and GTPase profiles associated with the class II peptide-loading compartment following BCR cross-linking. We first show that protein kinase inhibitors, known to block BCR signal transduction, inhibit BCR-enhanced antigen processing, demonstrating the critical dependence of enhanced processing on the signaling activity of the BCR. Consistent with this observation, the phosphoprotein profile of the class II peptide-loading compartment underwent rapid and transient changes following BCR cross-linking. We also observed a marked increase in the low mol. wt GTPases associated with the class II peptide-loading compartment within 5 min of BCR cross-linking. The observed changes in both the phosphoprotein and GTPase profiles associated with the peptide-loading compartment were blocked by kinase inhibitors and were not accompanied by overall gross changes in the protein composition of the subcellular compartments. Thus, signal cascades initiated by BCR cross-linking at the plasma membrane are translated into changes in specific subsets of regulatory proteins associated with the peptide-loading compartment.
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Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208, USA.
Press
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Wagle
N M
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Cho
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Wandinger-Ness
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Pierce
S K
SK
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D003432:Cross-Linking Reagents / Q000737:chemistry; D003574:Cytochrome c Group / Q000276:immunology; D020558:GTP Phosphohydrolases / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism*; D016393:Lymphoma, B-Cell; D051379:Mice; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D010750:Phosphoproteins / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured
D003432:Cross-Linking Reagents; D003574:Cytochrome c Group; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D020558:GTP Phosphohydrolases