ACCELERATION OF INTRACELLULAR TARGETING OF ANTIGEN BY THE B-CELL ANTIGEN RECEPTOR - IMPORTANCE DEPENDS ON THE NATURE OF THE ANTIGEN-ANTIBODY INTERACTION

The B-cell antigen receptor (BCR) internalizes bound antigen such that antigen-derived peptides become associated with emigrating major hist ocompatibility complex (MHC) class II molecules for presentation to T cells. Experiments with B-cell transfectants reveal that BCR confers a specificity of intracellular targeting since chimeric antigen recepto rs which internalize antigen by virtue of a heterologous cytoplasmic d omain do not necessarily give rise to presentation. In contrast, howev er, previous studies have shown that antigen binding to irrelevant cel l surface molecules (e.g. transferrin receptor, MHC class I) can ultim ately lead to presentation. The solution to this paradox appears to be that the intracellular targeting by BCR actually reflects an accelera tion of antigen delivery. Depending on the nature of the BCR-antigen i nteraction, this accelerated targeting can be essential in determining whether or not internalization leads to significant presentation. Phy siologically, the accelerated delivery of antigen by BCR could prove o f particular importance early in the immune response when antigen-BCR interaction is likely to be poor.