THE MONOMERIC GUANOSINE TRIPHOSPHATASE RAB4 CONTROLS AN ESSENTIAL STEP ON THE PATHWAY OF RECEPTOR-MEDIATED ANTIGEN-PROCESSING IN B-CELLS

Each member of the rab guanosine triphosphatase protein family assists in the regulation of a specific step within the biosynthetic or endoc ytic pathways. We have found that the early endosome-associated rab4 p rotein controls a step critical for receptor-mediated antigen processi ng in a murine A20 B cell Line. Expression of the dominant negative ra b4N(121)I mutant dramatically inhibited the processing and presentatio n of ovalbumin, lambda cI repressor, or rabbit immunoglobulin G intern alized as antigens by B cell antigen receptors or transfected Fc recep tors. This defect did not reflect a block in antigen endocytosis or de gradation, and transfected cells remained completely capable of presen ting exogenously added ovalbumin and lambda repressor peptides. Most r emarkably, rab4N(121)I-expressing cells were undiminished in their abi lity to present each of these antigens when whole proteins were intern alized at high concentration by fluid-phase endocytosis. Thus, express ion of the rab4N(121)I selectively inactivated a portion of the endocy tic pathway required for the processing of receptor-bound, but not non specifically internalized, antigens. These results suggest that elemen ts of the early endosome-recycling pathway play an important and selec tive role in physiologically relevant forms of antigen processing in B cells.