Activation of human B cells by phosphorothioate oligodeoxynucleotides.
To investigate the potential of DNA to elicit immune responses in man, we examined the capacity of a variety of oligodeoxynucleotides (ODNs) to stimulate highly purified T cell-depleted human peripheral blood B cells. Among 47 ODNs of various sequences tested, 12 phosphorothioate oligodeoxynucleotides (sODNs) induced marked B cell proliferation and Ig production. IL-2 augmented both proliferation and production of IgM, IgG, and IgA, as well as IgM anti-DNA antibodies, but was not necessary for B cell stimulation. Similarly, T cells enhanced stimulation, but were not necessary for B cell activation. After stimulation with the active sODNs, more than 95% of B cells expressed CD25 and CD86. In addition, B cells stimulated with sODNs expressed all six of the major immunoglobulin VH gene families. These results indicate that the human B cell response to sODN is polyclonal. Active sODN coupled to Sepharose beads stimulated B cells as effectively as the free sODN, suggesting that stimulation resulted from engagement of surface receptors. These data indicate that sODNs can directly induce polyclonal activation of human B cells in a T cell-independent manner by engaging as yet unknown B cell surface receptors.
Liang
H
H
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Nishioka
Y
Y
Reich
C F
CF
Pisetsky
D S
DS
Lipsky
P E
PE
D015703:Antigens, CD / Q000302:isolation & purification; D001402:B-Lymphocytes / Q000187:drug effects*; D051940:B7-2 Antigen; D002469:Cell Separation; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000302:isolation & purification; D008934:Mitogens / Q000494:pharmacology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2 / Q000302:isolation & purification; D013329:Structure-Activity Relationship; D013873:Thionucleotides / Q000494:pharmacology*
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D007136:Immunoglobulins; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D008934:Mitogens; D009838:Oligodeoxyribonucleotides; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D013873:Thionucleotides; D004247:DNA