The loss of Fc gamma RIIIb in paroxysmal nocturnal hemoglobinuria is
functionally replaced by Fc gamma RII
M Hundt, J Schubert, M de Haas, M Zielinska-Skowronek and RE Schmidt
Department of Medicine, Hannover Medical School, Germany.
Neutrophils from patients with paroxysmal nocturnal hemoglobinuria (PNH)
show a deficiency for the glycosylphosphatidylinositol- (GPI) linked Fc
gamma receptor IIIb (Fc gamma RIIIb, CD16). The functional consequences of
this defect are not clear. Here, we examined Fc gamma RIIIb-deficient
neutrophils for their activation via Fc gamma receptors. Hydrogen peroxide
(H2O2) production and change of intracellular free calcium [Ca2+]i were
used as parameters for cell activation. Fc gamma RII and Fc gamma RIIIb
stimulation was reached by cross-linking using fragments of monoclonal
antibodies or incubation with monoclonal IgG cryoglobulin complexes. In
parallel to the deficiency of Fc gamma RIIIb expression, H2O2 production
and [Ca2+]i influx were decreased after cross-linking of Fc gamma RIIIb in
PNH neutrophils compared with that for normal neutrophils. Stimulation via
Fc gamma RII was not affected. Cryoglobulin complexes previously shown to
activate normal neutrophils predominantly via Fc gamma RIIIb stimulated PNH
neutrophils at a level not significantly weaker than controls. But this
activation was mediated only via Fc gamma RII as shown by blocking studies.
The results suggest that the loss of GPI- anchored Fc gamma RIIIb is
functionally replaced by Fc gamma RII during the immune complex stimulation
of PNH neutrophils. Therefore, the equipment of neutrophils with
pleomorphic Fc gamma receptors prevents an immunodeficiency in PNH.
Volume 83,
Issue 12,
pp. 3574-3580,
06/15/1994
Copyright © 1994 by The American Society of Hematology
