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The Role of Surface Ig Binding in the Activation of Human B Cells by Phosphorothioate Oligodeoxynucleotides
Author(s) -
Liang H.,
Reich C. F.,
Pisetsky D. S.,
Lipsky P. E.
Publication year - 2001
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2001.01004.x
Subject(s) - immunoglobulin d , fluorescein isothiocyanate , receptor , polyclonal antibodies , antibody , microbiology and biotechnology , chemistry , biology , b cell , biochemistry , immunology , fluorescence , physics , quantum mechanics
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.