Syk tyrosine kinase and B cell antigen receptor (BCR) immunoglobulin-α subunit determine BCR-mediated major histocompatibility complex class II- restricted antigen presentation

Abstract

Stimulation of CD4+ helper T lymphocytes by antigen-presenting cells requires the degradation of exogenous antigens into antigenic peptides which associate with major histocompatibility complex (MHC) class II molecules in endosomal or lysosomal compartments. B lymphocytes mediate efficient antigen presentation first by capturing soluble antigens through clonally distributed antigen receptors (BCRs), composed of membrane immunoglobulin (Ig) associated with Ig-α/Ig-β heterodimers which, second, target antigens to MHC class II- containing compartments. We report that antigen internalization and antigen targeting through the BCR or its Ig-α-associated subunit to newly synthesized class II lead to the presentation of a large spectrum oft cell epitopes, including some cryptic T cell epitopes. To further characterize the intracellular mechanisms of BCR-mediated antigen presentation, we used two complementary experimental approaches: mutational analysis of the Ig-α cytoplasmic tail, and overexpression in B cells of dominant negative syk mutants. Thus, we found that the syk tyrosine kinase, an effector of the BCR signal transduction pathway, is involved in the presentation of peptide-MHC class II complexes through antigen targeting by BCR subunits.