Pathogenic effects of anti-Fc gamma receptor IIIb (CD16) on polymorphonuclear neutrophils in non-organ-specific autoimmune diseases.
The receptors FcgammaRIIIb and FcgammaRIIa for the Fc portion of IgG are naturally expressed in polymorphonuclear neutrophils (PMN). Autoantibodies (Ab) against FcgammaRIIIb 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 FcgammaRIIIb autoAbs, and an enzyme-linked immunosorbent assay for that of soluble FcgammaRIIIb-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 FcgammaRIIa and/or CD11b, the beta-chain of the neighboring complement receptor type 3. However, FcgammaRIIIb appears to be as competent as FcgammaRIIa, because the results obtained using the respective monoclonal Abs are additive. Soluble FcgammaRIIIb binds to CD11b and produces similar effects, suggesting that autoAb-stimulated FcgammaRIIIb can work in concert with CD11b. Anti-FcgammaRIIIb-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 FcgammaRIIIb, which may occur in patients with PMN-binding anti-FcgammaRIIIb autoAbs.
Youinou
Pierre
P
EA Immunologie et Pathologie, Brest University Medical School, BP 824, F29 609 Brest Cedex, France. youinou@univ-brest.fr
Durand
Véronique
V
Renaudineau
Yves
Y
Pennec
Yvon-Louis
YL
Saraux
Alain
A
Jamin
Christophe
C
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D006801:Humans; D018448:Models, Immunological; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D017452:Receptors, IgG / Q000097:blood / Q000276:immunology*
D015703:Antigens, CD; D001323:Autoantibodies; D017452:Receptors, IgG