Natural killer cell suppression of IgM production

The mechanisms by which natural killer (NK) cells regulate B cell function are not well understood. In this paper, the suppressive effects of NK cells on IgM production by lipopolysaccharide (LPS)-stimulated B cells were studied. We found that interleukin (IL)-2-activated NK (NKa) cells, but not unstimulated NK cells, suppressed IgM production by B cells stimulated with LPS. Suppression of antibody production required direct NKa-B cell contact, as demonstrated in cultures utilizing semiporous membranes for cell separation, and was the consequence of a reduction in the number of IgM-producing cells, as determined by enzyme-linked immunospot assays. Suppression could not be accounted for by cytotoxic mechanisms since the NKa cells caused neither cytolysis of 51Cr-labelled B cells or B cell apoptosis. While NKa-B cell contact was necessary for suppression, cell contact alone was not sufficient. Rather, both NKa-B cell contact and NKa production of interferon (IFN)-gamma were necessary. Since only IL-2-activated, but not unstimulated, NK cells suppressed IgM production, we investigated the potential for IL-4, which has been reported to downregulate IL-2-induced NK cell proliferation, to prevent NKa cell suppressive activity. While IL-4 antagonized IL-2-induced NK cell proliferation, it was completely ineffective in antagonizing NKa cell suppression of IgM production. The requirement for IL-2 activation of NK cells for suppression of IgM production suggests that NK cells may be part of a physiologic negative feedback mechanism to downregulate antibody production.