Receptor-Facilitated Antigen Presentation Requires the Recruitment of B Cell Linker Protein to Igα

Abstract

Ags that cross-link the B cell Ag receptor are preferentially and rapidly delivered to the MHC class II-enriched compartment for processing into peptides and subsequent loading onto MHC class II. Proper sorting of Ag/receptor complexes requires the recruitment of Syk to the phosphorylated immunoreceptor tyrosine-based activation motif tyrosines of the B cell Ag receptor constituent Igα. We postulated that the Igα nonimmunoreceptor tyrosine-based activation motif tyrosines, Y176 and Y204, contributed to receptor trafficking. Igα(YΔF176,204)/Igβ receptors were targeted to late endosomes, but were excluded from the vesicle lumen and could not facilitate the presentation of Ag to T cells. Subsequent analysis demonstrated that phosphorylation of Y176/Y204 recruited the B cell linker protein, Vav, and Grb2. Reconstitution of Igα(YΔF176,204)/Igβ with the B cell linker protein rescued both receptor-facilitated Ag presentation and entry into the MHC class II-enriched compartment. Thus, aggregation accelerates receptor trafficking by recruiting two separate signaling modules required for transit through sequential checkpoints.