Regulation of mucosal B cell immunoglobulin secretion by intestinal epithelial cell-derived cytokines

Intestinal epithelial cells (IEC) secrete a variety of cytokines and, becau se of their close proximity to B cells in the lamina propria, may affect lo cal antibody production via these cytokines, However, studies have not yet addressed which and to what extent these IEC-derived cytokines may affect B cell antibody production, In this study, rat mesenteric lymph node B cells were cultured with culture supernatants from the rat IEC-6 intestinal epit helial cell line to determine their effect on immunoglobulin (Ig) secretion . Unstimulated IEC-6 cells were found to secrete sufficient levels of IL-6 to enhance IgA, IgG and IgM secretion by unstimulated B cells. However, cul ture of lipopolysaccharide (LPS)-stimulated B cells with the unstimulated I EC-6 supernatant resulted in an enhancement of IgA secretion while IgM secr etion was significantly suppressed. Depletion of the IEC-6 supernatant usin g cytokine specific antibodies revealed that both interleukin 6 (IL-6) and transforming growth factor beta (TGF-beta) were responsible for the enhance d IgA secretion while TGF-beta suppressed IgM secretion, More importantly, culture supernatants from LPS stimulated IEC-6 cells contained enhanced lev els of IL-6 which enhanced both IBG and IgA production and partially overca me the suppressive effect of TGF-beta on IgM secretion. These results sugge st that intestinal epithelial cells may secrete IL-6 and TGF-beta to regula te local B cell antibody secretion and their effect may be highly dependent upon the activation state of the epithelial cells. (C) 1998 Academic Press .