The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/9/819/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 5, September 7, 1998 819-831

Articles

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

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

From * INSERM CJF 95-01, Institut Curie, Section Recherche, 75005 Paris, France; {ddagger} 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-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-{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

Address correspondence to C. Bonnerot, INSERM CJF 95-01, Institut Curie, Section Recherche, 12 rue Lhomond, 75005 Paris, France. Phone: 33-1-42-34-63-88; Fax: 33-1-42-34-63-82; E-mail: bonnerot{at}curie.fr

D. Lankar and V. Briken contributed equally to this work.

Abbreviations used: BCR, B cell antigen receptor; GST, glutathione S-transferase; HA, hemagglutinin; HEL, hen egg lysozyme; HRP, horseradish peroxidase; IC, immune complex(es); ITAM, immunoreceptor tyrosine–based activation motif; mIg, membrane immunoglobulin; PI3 kinase, phosphatidylinositol 3-kinase; PTK, phosphotyrosine kinase; SH2, src homology 2 domain.


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