Response of human platelets to activating monoclonal antibodies: Importance of Fc-γRII (CD32) phenotype and level of expression

Abstract

Certain monoclonal antibodies (MoAbs) specific for platelet membrane glycoproteins are known to be capable of activating platelets, and it is generally thought that platelets from normal subjects are equally susceptible to stimulation by such MoAbs. We found that platelets from 20 normal donors varied significantly in their sensitivity to three IgG1 murine MoAbs specific for membrane glycoproteins CD9, GPIV (CD36), and the GPIIb/IIIa complex (CD41), respectively. The response of platelets to these MoAbs was blocked by prior addition of MoAb IV.3 specific for the Fc-γRII receptor, indicating that activation was Fc receptor mediated. Platelets that responded poorly to these MoAbs failed to bind the MoAb 41H.16, specific for the "responder" form of FcγRII, but platelets that responded well reacted with this MoAb. The average number of FcfRII receptors on platelets from "responders" and "non-responders" was approximately the same. However, the number of Fc-γRII receptors expressed influenced sensitivity of a subgroup of "responder" platelets to the anti-CD41 MoAb. These platelets were judged on the basis of MoAb binding studies to be heterozygous for the two alleles of Fc-γRIIA. In contrast to their varying sensitivity to IgG1 MoAbs, members of the platelet panel responded equally well to 5OH.19, an IgG2a MoAb specific for CD9, and these responses could not be blocked by MoAb IV.3 in the presence of plasma. This appears to be because of dual actions of 50H.19 on platelets: one FcR-dependent and the other complement-dependent. Our findings confirm previous reports that certain IgG1 MoAbs activate platelets through binding of their Fc domains to Fc-γRII receptors and demonstrate that this response is influenced both by Fc-γRII phenotype and (in the case of the anti-CD41 MoAb) by the number of FcγRII receptors expressed. The failure of nonresponding platelets to bind detectable amounts of MoAb 41H.16, which is thought to recognize all Fc-γRII receptors except for one allele of the Fc-γRIIA gene, is consistent with the possibility that FcγRIIA gene products, but not FcγRIIC gene products, are expressed on platelets. © 1992 by The American Society of Hematology.