title: Ligation of HLA-DR molecules on B cells induces enhanced expression of IgM heavy chain genes in association with Syk activation.
abstract: Signals transmitted by class II major histocompatibility complex are important regarding cell function related to antigen presentation. We examined effects of DR-mediated signaling on Ig production from B cells. Cross-linking HLA-DR molecules on B cells by solid-phase anti-HLA-DR monoclonal antibodies, led to an increased production of IgM, without proliferation or apoptosis. This event was accompanied by an enhanced expression of both membrane- and secretory-type IgM heavy chain mRNA. When peptide-pulsed B cells were co-incubated with an HLA-DR-restricted T cell clone treated by the protein synthesis inhibitor emetine, peptide-induced de novo expression of lymphokines and cell-surface molecules on T cells can be neglected. CD40-CD154 interaction was not involved in IgM enhancement, in such a system. The protein-tyrosine kinase inhibitors and the Syk inhibitor piceatannol, but not the Src inhibitor PP2 had a marked inhibitory effect on IgM secretion. Furthermore, ligation of HLA-DR on B cells using the F(ab')2 fragment of anti-DR monoclonal antibody, enhanced Syk activity. Our data suggest that HLA-DR on B cells not only present antigenic peptides to T cells, but also up-regulate IgM production, in association with Syk activation and without the involvement of Src kinases, hence the possible physiological relevance of Src-independent Syk activation.
authors.affiliation: Division of Immunogenetics, Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences and the Department of Pediatrics, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tabata
authors.forename: T
authors.initials: T
authors.lastname: Matsuoka
authors.forename: F
authors.initials: F
authors.lastname: Endo
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
authors.forename: S
authors.initials: S
authors.lastname: Matsushita
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D002455:Cell Division; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004640:Emetine / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D047908:Intracellular Signaling Peptides and Proteins; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D017304:Annexin A5; D019013:CD40 Antigens; D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D006684:HLA-DR Antigens; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D047908:Intracellular Signaling Peptides and Proteins; D008222:Lymphokines; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D013267:Stilbenes; D023201:CD40 Ligand; C041525:3,3',4,5'-tetrahydroxystilbene; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D004640:Emetine