Macrophage-derived TGF-beta1 induces IgA isotype expression.
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.
Min
Kyoung-Mi
KM
Department of Microbiology, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Korea.
Kim
Pyeung-Hyeun
PH
D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000276:immunology*; D017578:Immunoglobulin Class Switching / Q000187:drug effects / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D007070:Immunoglobulin A; D007132:Immunoglobulin Isotypes; D007376:Interleukin-2; D008070:Lipopolysaccharides; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma