Ig alpha and Ig beta are required for efficient trafficking to late endosomes and to enhance antigen presentation.

The B cell Ag receptor (BCR) is a multimeric complex, containing Ig alpha and Ig beta, capable of internalizing and delivering specific Ags to specialized late endosomes, where they are processed into peptides for loading onto MHC class II molecules. By this mechanism, the presentation of receptor-selected epitopes to T cells is enhanced by several orders of magnitude. Previously, it has been reported that, under some circumstances, either Ig alpha or Ig beta can facilitate the presentation of Ags. However, we now demonstrate that if these Ags are at low concentrations and temporally restricted, both Ig alpha and Ig beta are required. When compared with the BCR, chimeric complexes containing either chain alone were internalized but failed to access the MHC class II-enriched compartment (MIIC) or induce the aggregation and fusion of its constituent vesicles. Furthermore, Ig alpha/Ig beta complexes in which the immunoreceptor tyrosine-based activation motif tyrosines of Ig alpha were mutated were also incapable of accessing the MIIC or of facilitating the presentation of Ag. These data indicate that both Ig alpha and Ig beta contribute signaling, and possibly other functions, to the BCR that are necessary and sufficient to reconstitute the trafficking and Ag-processing enhancing capacities of the intact receptor complex.