Pathogenic effects of anti-Fc gamma receptor IIIb (CD16) on polymorphonuclear neutrophils in non-organ-specific autoimmune diseases

The receptors FcγRIIIb and FcγRIIa for the Fc portion of IgG are naturally expressed in polymorphonuclear neutrophils (PMN). Autoantibodies (Ab) against FcγRIIIb exist in patients with non-organ-specific disease. These may be categorized, based on the results of an indirect immunofluorescence (IIF) test for the detection of anti-membrane-bound FcγRIIIb autoAbs, and an enzyme-linked immunosorbent assay for that of soluble FcγRIIIb-recognizing autoAbs. The IIF+ autoAbs are not cytotoxic, and prolong the survival of the cells. The autoAb-triggered anti-apoptotic signal may be transduced through FcγRIIa and/or CD11b, the β-chain of the neighboring complement receptor type 3. However, FcγRIIIb appears to be as competent as FcγRIIa, because the results obtained using the respective monoclonal Abs are additive. Soluble FcγRIIIb binds to CD11b and produces similar effects, suggesting that autoAb-stimulated FcγRIIIb can work in concert with CD11b. Anti-FcγRIIIb-conditioned supernatant of PMNs induces the transcription of messenger RNA for granulocyte colony-stimulating factor (CSF) and granulocyte-macrophage CSF, followed by the release of these anti-apoptotic factors. The delay in apoptosis is accompanied by a down-regulated expression of Bax. Thus, apoptosis of aged PMNs can be modulated by signaling through FcγRIIIb, which may occur in patients with PMN-binding anti-FcγRIIIb autoAbs.