Signaling through the B cell antigen receptor regulates discrete steps in the antigen processing pathway.
Antigen processing in B cells is initiated by antigen binding to the surface B cell antigen receptor (BCR). The BCR is a signaling receptor which also functions to endocytose bound antigen for subsequent intracellular processing and presentation with class II molecules. Previously, using subcellular fractionation, we showed that although the surface BCR constitutively traffics from the cell surface to the class II peptide-loading compartment (IIPLC), cross-linking the BCR regulates trafficking, resulting in a more rapid movement of the BCR to the IIPLC (Song et al., 1995, J. Immunol. 155, 4255). The rate of degradation of both the BCR and the bound antigen was also accelerated following BCR cross-linking. Here we provide evidence that the effect of cross-linking the BCR on antigen processing is in part dependent on signal cascades initiated by the BCR. We show that the protein kinase inhibitors Genistein and Chelerythrine, which block BCR signaling, reduce BCR-enhanced antigen processing in a dose-dependent manner. The kinase inhibitors have a small effect on the rate of internalization of the BCR and antigen following BCR cross-linking and significantly decrease the accelerated trafficking to the IIPLC. The increased rate of degradation of the BCR and antigen induced by BCR cross-linking is also decreased by the kinase inhibitors. BCR signaling does not appear to have a global effect on intracellular membrane trafficking as cross-linking the BCR did not alter the rate of trafficking of newly synthesized class II molecules to the IIPLC. Thus, the signaling function of the BCR appears to play a significant role in regulating discrete steps in the intracellular antigen processing pathway.
Wagle
N M
NM
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
Kim
J H
JH
Pierce
S K
SK
D000470:Alkaloids; D000818:Animals; D017951:Antigen Presentation; D053119:Benzophenanthridines; D002227:Carbazoles; D019833:Genistein / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D010617:Phenanthridines / Q000494:pharmacology; D011494:Protein Kinases / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism / Q000502:physiology*
D000470:Alkaloids; D053119:Benzophenanthridines; D002227:Carbazoles; D000949:Histocompatibility Antigens Class II; D007211:Indoles; D010617:Phenanthridines; D011758:Pyrroles; D011947:Receptors, Antigen, B-Cell; C057416:KT 5720; D019833:Genistein; C016299:chelerythrine; D011494:Protein Kinases