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J. Exp. Med., Volume 188, Number 5, September 7, 1998 819-831

Syk Tyrosine Kinase and B Cell Antigen Receptor (BCR) Immunoglobulin-alpha Subunit Determine BCR-mediated Major Histocompatibility Complex Class II-restricted Antigen Presentation

By Danielle Lankar,* Volker Briken,* Kristin Adler,* Peter Weiser,* Sylvanie Cassard,* Ulrich Blank,Dagger Mireille Viguier,§ and Christian Bonnerot*

From * INSERM CJF 95-01, Institut Curie, Section Recherche, 75005 Paris, France; Dagger  Unité d'Immuno-allergie, Institut Pasteur, 75015 Paris, France; and § Laboratoire d'Immunologie des Pathologies Infectieuses et Tumorales, Institut Cochin de Genetique Moleculaire, INSERM U445, 75013 Paris, France

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-alpha /Ig-beta 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-alpha -associated subunit to newly synthesized class II lead to the presentation of a large spectrum of T 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-alpha 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.

Key words: B cell receptor;  syk tyrosine kinase;  antigen presentation;  major histocompatibility complex class II;  immunoglobulin


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