Human Natural Killer Clones Enhance in Vitro Antibody Production by Tumour Necrosis Factor Alpha and Gamma Interferon

Abstract

To determine whether NK cells are involved in the regulation of the antibody response, we studied the effects of human NK clones on B-cell growth and differentiation and the mechanisms involved. We demonstrate that various human NK clones enhance the immunoglobulin production of SAC/rIL-2-activated B cells, e.g. IgG and IgM by up to 230% and anti-tetanus toxoid antibodies by up to 430%. Cell-cell interactions via cell-surface structures, e.g. the CD11a/CD18 molecule, were found to be critical. Subsequently the NK-mediated B-cell regulation involves cytokines, since cell-free supernatants obtained by 48-h cultures of NK clones exerted BCGF and BCDF activity. Neutralization studies and direct determination characterized these cytokines as IFN-gamma and TNF-alpha. The cytokine production of NK clones could be triggered by activated B cells only. Northern blot analysis demonstrated that activated B cells in co-culture with NK clones were able to induce accumulation of mRNA transcripts for IFN-gamma and TNF-alpha in NK cells.