Effect of intestinal epithelial cell cytokines on mucosal B-cell IgA secretion: enhancing effect of epithelial-derived IL-6 but not TGF-beta on IgA+ B cells

A variety of cell types may be involved in the regulation of IgA secretion at the intestinal mucosa. Intestinal epithelial cells (IEC) are known to have the capacity to secrete several cytokines which may exert an important regulatory effect on local immunoglobulin secretion by mucosal B cells. In this study, we have determined the effect of secreted cytokines from the rat non-transformed IEC-6 cell line on IgA secretion by IgA+ mesenteric lymph node B cells. Four day IEC-6 cell culture supernatants (SN) were found to enhance lipopolysaccharide (LPS) stimulated IgA secretion by 3-fold and this enhancement was determined to be due to IEC-derived IL-6. Interestingly, IEC-derived TGF-beta as well as recombinant human latent TGF-beta1 were found to have no effect on IgA secretion by the IgA+ B cells suggesting that these cells may be insensitive to the latent form of this cytokine. Finally, the addition of a culture SN from a 5 h culture of isolated normal rat IEC which contained high levels of IL-6 also greatly enhanced IgA secretion by LPS stimulated IgA+ B cells. These results suggest that the IEC may be an important source of IL-6 to enhance local mucosal IgA+ B cell responses.