Retinoids enhance IgA production by lipopolysaccharide-stimulated murine spleen cells.

The effect of all-trans retinoic acid (RA) and vitamin A on IgA production by LPS-stimulated murine spleen cells was studied. Concentrations of immunoglobulins of six subclasses in the culture medium were determined. Only IgA level increased, RA dose dependently. In contrast, IgG1 level decreased and other subclasses (IgM, IgG2a, IgG2b, and IgG3) were not significantly affected by the treatment. IgA levels in LPS-stimulated spleen cells were usually between 10 and 100 ng/ml. When RA was added at the concentrations above 0.1 nM, the levels were increased dose dependently and peak response (8- to 20-fold) was observed from 0.1 to 1 microM. Enhancement of IgA secretion begins after 4 days culture and then increases linearly until Day 7. Vitamin A also showed IgA-enhancing activity, although its activity was about 1/170 of that of RA. TGF-beta activity in the culture medium was also determined, finding that RA rapidly stimulates secretion of biologically active TGF-beta, the elevation being evident after 1 day of culture. Specific neutralizing antibodies to TGF-beta 1 and TGF-beta 2 partially inhibited IgA enhancement caused by RA. These results suggest that retinoids at physiological concentrations may act as positive regulators for IgA production and the effect may be mediated, at least in part, via the induction of active TGF-beta.