Macrophage-derived TGF-β1 Induces IgA Isotype Expression

TGF-β1 is a potent IgA isotype switching factor. However the cell population that generates the TGF-β is not known. In this study, we examined the origin of the TGF-β1 that is secreted by LPS-activated murine total spleen cell cultures and that is responsible for IgA isotype switching. Treatment with anti-TGFβ1 antibody decreased IgA secretion 2 fold in these cultures and caused a 5-fold decrease in the number of IgA secreting cells. In Mφ-depleted spleen cell populations, this IgA response was markedly reduced and anti-TGFβ1 antibody had no additional effect on IgA production. The inference that Mφ-derived TGF-β1 is responsible for the isotype switching is supported by observations with the macrophage line, P388D1. LPS, particularly in the presence of IFN-γ, induced P388D1 cells to secrete active TGF-β1. The supernatant from such an activated P388D1 culture, in combination of IL-2, stimulated IgA secretion and this effect was abolished by anti-TGFβ1 antibody.