Activation of Human B Cells by Phosphorothioate Oligodeoxynucleotides

J Clin Invest. 1996 Sep 1;98(5):1119-29. doi: 10.1172/JCI118894.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / isolation & purification
  • B-Lymphocytes / drug effects*
  • B7-2 Antigen
  • Cell Separation
  • Cells, Cultured
  • DNA / immunology
  • DNA / pharmacology*
  • Flow Cytometry
  • Humans
  • Immunoglobulins / biosynthesis
  • Interleukin-2 / pharmacology
  • Lymphocyte Activation*
  • Membrane Glycoproteins / isolation & purification
  • Mitogens / pharmacology
  • Oligodeoxyribonucleotides / pharmacology*
  • Polymerase Chain Reaction
  • Receptors, Immunologic
  • Receptors, Interleukin-2 / isolation & purification
  • Structure-Activity Relationship
  • Thionucleotides / pharmacology*

Substances

  • Antigens, CD
  • B7-2 Antigen
  • CD86 protein, human
  • Immunoglobulins
  • Interleukin-2
  • Membrane Glycoproteins
  • Mitogens
  • Oligodeoxyribonucleotides
  • Receptors, Immunologic
  • Receptors, Interleukin-2
  • Thionucleotides
  • DNA