Overexpression of rab7 enhances the kinetics of antigen processing and presentation with MHC class II molecules in B cells.
rab7 is an intracellular GTPase involved in early to late endosome fusion. By overexpressing rab7 in a B lymphoma we show that the rate of antigen presentation with MHC class II molecules is increased for four different peptide-MHC combinations, under conditions where levels of other components of the antigen-processing pathway remained constant. Resting B cells were shown to express significantly lower levels of rab7 when compared to adherent macrophages or to 'immature' or 'mature' dendritic cells. rab7 expression was up-regulated by stimulation of B cells with lipopolysaccharide or CD40 ligand. Other components of the endocytic pathway were also up-regulated in activated B cells, suggesting that B cell activation leads to a general enlargement of the endocytic compartment, correlating with the increased ability of activated B cells to process antigen. Taken together, our results suggest that rab7 levels regulate the rate of antigen presentation in B cells, and that rab7 and late endocytic compartments are important in MHC class II-restricted antigen presentation in B cells.
Bertram
Edward M
EM
Department of Immunology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Hawley
Robert G
RG
Watts
Tania H
TH
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D011485:Protein Binding; D014162:Transfection; D014407:Tumor Cells, Cultured; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
D000949:Histocompatibility Antigens Class II; D000090802:rab7 GTP-Binding Proteins; C000716465:rab7 GTP-binding proteins, mouse; D000643:Ammonium Chloride; D020691:rab GTP-Binding Proteins