Consequences of Fcγ receptor type III reactivity in non-organ-specific autoimmune diseases

Abstract

Polymorphonuclear neutrophils (PMNs) express constitutively the Fcγ receptors (FcγRs) FcγRIIIb and FcγRIIa for the Fc part of IgG, and soluble FcγRIIIb (sFcγRIIIb) has been identified. Elevated levels of sFcγRIIIb were detected in non-organ-specific autoimmune conditions, and there was a considerably decreased number of PMNs undergoing apoptosis in the presence of sFcγRIIIb. Anti-FcγRIIIb autoantibodies (autoAbs) have also been described in such patients. They are not cytotoxic to these cells, but they extend their survival. The anti-apoptotic signal can be transduced through FcγRIIa and/or CD11b, the β-chain of the complement receptor 3. However, FcγRIIIb appears to be also competent. Anti-FcγRIIIb-conditioned supernatant from cultured PMNs induces the transcription of messenger RNA for granulocyte colonystimulating factor and granulocyte/macrophage colony-stimulating factor, followed by protein synthesis. The delay in apoptosis may be generated by a downregulation of the death promoter Bax. Inflammation might thus be modulated by sFcγRIIIb and anti-FcγRIIIb autoAbs in systemic diseases.