Selective induction of rheumatoid factors by superantigens and human helper T cells

X. He, J. Goronzy, C. Weyand

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Production of autoantibodies specific for the Fc region of autologous IgG, called rheumatoid factors (RF), is a characteristic finding in patients with rheumatoid arthritis (RA). To study the requirements regulating the synthesis of these autoantibodies, we have cloned human helper T cells and co-cultured them with purified B cells. To mimic cognate T-B cell interaction, we have used bacterial superantigens that function by cross-linking HLA molecules on the B cell with selected T cell receptor (TCR) molecules expressing a particular polymorphism of the Vβ gene segment. Data presented here demonstrate that the staphylococcal enterotoxin D (SE D), but not other bacterial superantigens, exhibits an ability to induce IgM, IgG, and especially RF production, in B cells from RA patients and normal individuals. Comparison with the polyclonal antibody production in B cell cultures driven by anti-CD3-stimulated T cell clones confirmed that SE D shifted the repertoire of secreted antibodies toward immunoglobulins with Fc binding specificity, suggesting that SE D preferentially stimulates RF+ B lymphocytes. B cells with the potential to secrete RF were highly frequent in RA patients, requiring as few as 150 peripheral B cells/culture to detect RF in the culture supernatants. SE D-induced RF synthesis was strictly dependent on the presence of selected CD4+T helper cells and required a direct membrane contact between B cells and T helper cells. Here, we propose a model that SE D selectively induces RF production depending on the availability of SE D responsive T cells in the TCR repertoire of the responder.

Original languageEnglish (US)
Pages (from-to)673-680
Number of pages8
JournalJournal of Clinical Investigation
Volume89
Issue number2
DOIs
StatePublished - 1992

Keywords

  • B cell regulation
  • Rheumatoid arthritis
  • Rheumatoid factor
  • Staphylococcal enterotoxin

ASJC Scopus subject areas

  • Medicine(all)

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