NATURAL-KILLER-CELLS INDUCE ACTIVATED MURINE B-CELLS TO SECRETE IG

We previously demonstrated that dextran-conjugated anti-IgD antibodies (alphadelta-dex) induce proliferation of small, B cell-enriched murin e spleen cells (B(e) cells), and in the presence of IL-2, stimulate Ig secretion in vitro. We have shown that alphadelta-dex-stimulated B ce lls provide an in vitro model for studying B cell activation by T cell -independent type 2 (TI-2) Ag, as exemplified by the bacterial polysac charides. We now show that highly purified resting B cells, obtained b y electronic cell sorting (B(sp) cells), fail to secrete Ig in the pre sence of alphadelta-dex + IL-2. The alphadelta-dex + IL-2-induced Ig s ecretory response of B(sp) cells is restored upon addition of splenic non-B, non-T cells or a pure population of in vitro-generated NK cells . Similarly, pretreatment of B(e) cells with anti-AsGm-1 plus compleme nt inhibits Ig secretion in response to alphadelta-dex + IL-2. An IL-2 -induced NK cell supernatant (NKSN) is equally potent at stimulating I g secretion by alphadelta-dex-activated BsP cells, indicating that cel l contact between B(sp) and activated NK cells is not required for thi s effect. IL-2 stimulates not only NK cells, but B cells as well, sinc e addition of anti-IL-2 + anti-IL-2R antibodies to B(sp) cell cultures , in the presence of alphadelta-dex + NKSN, inhibits Ig secretion. The se data describe a novel animal model for NK cell-induced B cell matur ation to Ig secretion and suggest a pathway for Ig production in respo nse to TI-2 Ag.