Macrophage-derived TGF-beta1 induces IgA isotype expression

Mol Cells. 2003 Oct 31;16(2):245-50.

Abstract

TGF-beta1 is a potent IgA isotype switching factor. However the cell population that generates the TGF-beta is not known. In this study, we examined the origin of the TGF-beta1 that is secreted by LPS-activated murine total spleen cell cultures and that is responsible for IgA isotype switching. Treatment with anti-TGFbeta1 antibody decreased IgA secretion 2 fold in these cultures and caused a 5-fold decrease in the number of IgA secreting cells. In Mphi-depleted spleen cell populations, this IgA response was markedly reduced and anti-TGFbeta1 antibody had no additional effect on IgA production. The inference that Mphi-derived TGF-beta1 is responsible for the isotype switching is supported by observations with the macrophage line, P388D1. LPS, particularly in the presence of IFN-gamma, induced P388D1 cells to secrete active TGF-beta1. The supernatant from such an activated P388D1 culture, in combination of IL-2, stimulated IgA secretion and this effect was abolished by anti-TGFbeta1 antibody.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody-Producing Cells / drug effects
  • Antibody-Producing Cells / immunology*
  • Antibody-Producing Cells / metabolism
  • Cells, Cultured
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin A / immunology*
  • Immunoglobulin Class Switching / drug effects
  • Immunoglobulin Class Switching / immunology
  • Immunoglobulin Isotypes / immunology
  • Immunoglobulin Isotypes / metabolism
  • Interferon-gamma / pharmacology
  • Interleukin-2 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Spleen
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta1

Substances

  • Immunoglobulin A
  • Immunoglobulin Isotypes
  • Interleukin-2
  • Lipopolysaccharides
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Interferon-gamma