SYK TYROSINE KINASE AND B-CELL ANTIGEN RECEPTOR (BCR) IMMUNOGLOBULIN-ALPHA SUBUNIT DETERMINE BCR-MEDIATED MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II RESTRICTED ANTIGEN PRESENTATION

Stimulation of CD4(+) helper T lymphocytes by antigen-presenting cells requires the degradation of exogenous antigens into antigenic peptide s which associate with major histocompatibility complex (MHC) class II molecules in endosomal or lysosomal compartments. B lymphocytes media te efficient antigen presentation first by capturing soluble antigens through clonally distributed antigen receptors (BCRs), composed of mem brane immunoglobulin (Ig) associated with Ig-alpha/Ig-beta heterodimer s which, second, target antigens to MHC class II-containing compartmen ts. We report that antigen internalization and antigen targeting throu gh the BCR or its Ig-alpha-associated subunit to newly synthesized cla ss II lead to the presentation of a large spectrum of T cell epitopes, including some cryptic T cell epitopes. To further characterize the i ntracellular mechanisms of BCR-mediated antigen presentation, we used two complementary experimental approaches: mutational analysis of the Ig-alpha cytoplasmic tail, and overexpression in B cells of dominant n egative syk mutants. Thus, we found that the syk tyrosine kinase, an e ffector of the BCR signal transduction pathway, is involved in the pre sentation of peptide-MHC class II complexes through antigen targeting by BCR subunits.