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To determine whether N K 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/rlL-2-activated B cells, e.g. IgG and IgM by up to 23% and anti-tetanus toxoid antibodies by up to430%.Cell cell interactions via cell-surface structures. e.g. the CD11a/ CDI8 molecule, were found lo 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-γ and TNF-α. 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-γ and TNF-α in NK cells. [ABSTRACT FROM AUTHOR]