title: The monomeric guanosine triphosphatase rab4 controls an essential step on the pathway of receptor-mediated antigen processing in B cells.
abstract: Each member of the rab guanosine triphosphatase protein family assists in the regulation of a specific step within the biosynthetic or endocytic pathways. We have found that the early endosome-associated rab4 protein controls a step critical for receptor-mediated antigen processing in a murine A20 B cell line. Expression of the dominant negative rab4N121I mutant dramatically inhibited the processing and presentation of ovalbumin, lambda cI repressor, or rabbit immunoglobulin G internalized as antigens by B cell antigen receptors or transfected Fc receptors. This defect did not reflect a block in antigen endocytosis or degradation, and transfected cells remained completely capable of presenting exogenously added ovalbumin and lambda repressor peptides. Most remarkably, rab4N121I-expressing cells were undiminished in their ability to present each of these antigens when whole proteins were internalized at high concentration by fluid-phase endocytosis. Thus, expression of the rab4N121I selectively inactivated a portion of the endocytic pathway required for the processing of receptor-bound, but not nonspecifically internalized, antigens. These results suggest that elements of the early endosome-recycling pathway play an important and selective role in physiologically relevant forms of antigen processing in B cells.
authors.affiliation: Department of Cell Biology, Yale University Medical Center, New Haven, Connecticut 06520-8002, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Lazzarino
authors.forename: P
authors.initials: P
authors.lastname: Blier
authors.forename: I
authors.initials: I
authors.lastname: Mellman
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D004268:DNA-Binding Proteins; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000235:genetics; D010047:Ovalbumin / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology; D012097:Repressor Proteins / Q000276:immunology; D014162:Transfection / Q000235:genetics; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; D020695:rab4 GTP-Binding Proteins
chemical_list: D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D011961:Receptors, Fc; D012097:Repressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins; D010047:Ovalbumin; D019204:GTP-Binding Proteins; D020695:rab4 GTP-Binding Proteins