Transforming growth factor β1 selectivity stimulates immunoglobulin G2b secretion by lipopolysaccharide-activated murine B cells

Tina M. McIntyre, Dennis R. Klinma, Paul Rohman, Michelle Lugo, James R. Dasch, James J. Mond, Clifford M. Snapper

Research output: Contribution to journalArticlepeer-review

Abstract

Bacterial lipopolysaccharide (LPS) has been reported to induce immunoglobulin (Ig)G2b class switching, yet we observed strain differences in IgG2b secretion in response to this mitogen. Specifically, BALB/c B cells, unlike those from DBA/2, synthesized relatively low amounts of IgG2b relative to IgG3, IgG1, or IgM. This report demonstrates that transforming growth factor (TGF)α1, previously shown to induce IgA dass switching, selectively stimulates IgG2b secretion by BALB/c resting B cells activated with LPS. This activity was specifically reversed with a neutralizing anti-TGF-α1 antibody. The ability of TGF-α1 to act directly on highly purified membrane (m)IgM+mlgG2b - cells to stimulate IgG2b production, stimulate an increase in IgG2b-secreting cells, and selectively increase the steady-state levels of germline γ2b RNA, suggests that it promotes IgG2b class switching. In this regard, addition of anti-TGF-γ antibody to cultures of DBA/2-derived resting B cells activated by LPS, alone, led to selective reduction in IgG2b secretion, indicating that endogenous TGF-α1 accounts for the high IgG2b secretory response observed in that strain. Finally, TGF-α1 failed to stimulate IgG2b secretion by B cells activated with dextran-conjugated anti-IgD antibody. We propose that TGF-α1 is a switch factor for the murine IgG2b subclass for appropriately activated B cells. In combination with other data, this would show that all six non-IgM, non-IgD isotypes in the mouse can be selectively induced by specific cytokines.

Original languageEnglish (US)
Pages (from-to)1031-1037
Number of pages7
JournalJournal of Experimental Medicine
Volume177
Issue number4
DOIs
StatePublished - Apr 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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