Preferential enhancement of B cell IgA secretion by intestinal epithelial cell-derived cytokines and interleukin-2

Intestinal epithelial cells (IEC) are known to secrete a number of importan t cytokines. Recently, we determined that IEC-derived IL-6 and TGF-beta cou ld enhance IgA secretion and suppress IgM secretion by isolated mucosal B c ells. However, since the IEC-derived cytokines must function in the context of locally produced T cell cytokines, the effect of IEC- and T cell-derive d cytokines on mucosal B cell immunoglobulin secretion was determined. Usin g 4 day culture supernatants (IEC-SN) from the rat IEC-6 intestinal epithel ial cell line and lipopolysaccharide (LPS) stimulated Peyer's patch or mese nteric lymph node B cells, the IEC-SN was found to act with IL-2 to greatly enhance IgA secretion but limit br suppress IgM secretion as compared to c ultures of LPS stimulated B cells alone. However, neither IL-4, IL-5, nor I FN-gamma affected IgA secretion with the IEC-SN. Depletion of the IEC-SN wi th specific anti-cytokine antibodies suggested that IEC-derived TGF-beta an d IL-6 were both responsible for the enhancing effect along with IL-2 on Ig A secretion, whereas IEC-derived TGF-beta alone limited or suppressed IgM s ecretion. These results suggest that cytokines derived from local IEC and T cells may create an environment which may contribute to the preferential e nhancement of IgA secretion seen in mucosal tissues.