The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/11/1769/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 10, November 16, 1998 1769-1774

Articles

The Monomeric Guanosine Triphosphatase rab4 Controls an Essential Step on the Pathway of Receptor-mediated Antigen Processing in B Cells

Deborah A. Lazzarino*,{ddagger}, Peter Blier{ddagger}, and Ira Mellman*

From the * Department of Cell Biology, Yale University Medical Center, New Haven, Connecticut 06520-8002; and {ddagger} Boehringer-Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877

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.

Key Words: endocytosis • endosomes • B cell • major histocompatibility complex class II • recycling

Address correspondence to Ira Mellman, Department of Cell Biology, Yale University Medical Center, 333 Cedar St., PO Box 208002, New Haven, CT 06520-8002. Phone: 203-785-4303; Fax: 203-785-4301; E-mail: ira.mellman{at}yale.edu

Flow cytometry was expertly performed by Rocco Carbone. For generosity with reagents and helpful advice throughout this work we thank David Lewin, Stacey Minskoff, Alisa Kabcenell, Sebastian Amigorena, and Jim Drake.

Abbreviations used: BCR, B cell receptor; DNP, dinitrophenyl; HRP, horseradish peroxidase; TfnR, transferrin receptor; WT, wild-type.


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