The role of surface ig binding in the activation of human B cells by phosphorothioate oligodeoxynucleotides.
Phosphorothioate oligodeoxynucleotides (sODNs) can induce T-cell-independent polyclonal activation of human B cells by a mechanism that depends on both sequence and back-bone structure. Because matrix-bound as well as soluble sODNs are mitogenic, this stimulation may result from the engagement of surface receptor(s). In order to investigate whether surface immunoglobin (Ig) could be a receptor for sODNs, the interaction of sODNs-fluorescein isothiocyanate (FITC) with Ig-coated beads was examined. sODNs specifically bound to human IgM and IgG. Moreover, binding of sODN to human B cells induced temperature-dependent capping of bound receptors and colocalization of FITC-sODN and IgM into aggregated caps on the surface of human B cells. A role of surface Ig was furthermore shown by observations that antibody-mediated capping of B-cell surface IgM or IgD inhibited subsequent binding of sODNs and that the capacity of sODN to stimulate human B cells was blocked by excess IgM or IgG, by nonstimulatory antibodies to sIgM, as well as by a variety of negatively charged molecules. Together, these results indicate that sODNs engage surface Ig by charge-charge interactions that lead to activation of human B cells.
Liang
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Harold C. Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas South-western Medical Center, Dallas 75235, USA.
Reich
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Pisetsky
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Lipsky
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D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D001483:Base Sequence; D006678:HIV / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007152:Immunologic Capping / Q000187:drug effects; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D008934:Mitogens / Q000494:pharmacology; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000071228:Polyelectrolytes; D011108:Polymers / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D013873:Thionucleotides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008934:Mitogens; D009838:Oligodeoxyribonucleotides; D000071228:Polyelectrolytes; D011108:Polymers; D011947:Receptors, Antigen, B-Cell; D013873:Thionucleotides