Ligation of HLA-DR molecules on B cells induces enhanced expression of IgM heavy chain genes in association with Syk activation.
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.
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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.
Matsuoka
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T
Endo
F
F
Nishimura
Y
Y
Matsushita
S
S
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
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