A novel lymphokine derived from human IgG Fc receptor-bearing B cells: its suppressive effect on activated T and B lymphocytes including tumour cells in vitro.

Peripheral blood FcR gamma-bearing human B cells, but neither T cells nor adherent cells, produce an immunoregulatory lymphokine after receiving the stimulation of FcR gamma by immune complexes--antibody-sensitized erythrocytes (EA). This factor suppresses polyclonal immunoglobulin (Ig) production of B cells to pokeweed mitogen (PWM) and Nocardia opaca delipidated cell mitogen (NDCM), indicating that not only B cells, but also T cells are targets for this factor. It also inhibits the proliferation of mitogen-activated mononuclear and T and B tumour cells in vitro. The inhibitory effect on tumour cell growth is cytostatic, but not cytotoxic as in the case of lymphotoxin (LT). All these suppressive effects are observed in a HLA-non-restricted manner. Irradiation (2000 rads) of FcR gamma + B cells does not inhibit the production of this suppressive factor, implying that DNA synthesis is unnecessary. Nonstimulated FcR gamma + B cells retain the precursor activity for Ig-forming cells, since mononuclear cells untreated with EA respond to the mitogens, resulting in Ig production. However, it is worthy to note that they lose the activity when stimulated with immune complexes. Thus, the property obtained from human FcR gamma + B cells is similar to, but distinct from, a murine suppressive B-cell factor (SBF) prepared by the same procedure as for the human factor. Nevertheless, the observation in the present studies on the human analogue to murine SBF suggests that this factor, tentatively termed human SBF, appears to be a novel lymphokine which is different from any other factors, including LT, and that FcR-bearing B cells play an important role in the immunoregulatory mechanism in humans, as in the case of mice.