Regulation of mucosal B cell immunoglobulin secretion by intestinal epithelial cell-derived cytokines.
Intestinal epithelial cells (IEC) secrete a variety of cytokines and, because of their close proximity to B cells in the lamina propria, may affect local 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 epithelial 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, culture of lipopolysaccharide (LPS)-stimulated B cells with the unstimulated IEC-6 supernatant resulted in an enhancement of IgA secretion while IgM secretion was significantly suppressed. Depletion of the IEC-6 supernatant using cytokine specific antibodies revealed that both interleukin 6 (IL-6) and transforming growth factor beta (TGF-beta) were responsible for the enhanced IgA secretion while TGF-beta suppressed IgM secretion. More importantly, culture supernatants from LPS stimulated IEC-6 cells contained enhanced levels of IL-6 which enhanced both IgG and IgA production and partially overcame the suppressive effect of TGF-beta on IgM secretion. These results suggest that intestinal epithelial cells may secrete IL-6 and TGF-beta to regulate local B cell antibody secretion and their effect may be highly dependent upon the activation state of the epithelial cells.
Department of Biological Sciences, Binghamton University (SUNY), Binghamton, NY 13902-6000, USA.
M E
ME
Goodrich
D W
DW
McGee
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000494:pharmacology*; D004848:Epithelium / Q000276:immunology; D005260:Female; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D017077:Culture Media, Conditioned; D016207:Cytokines; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta; C033027:secretory IgM