Relationship between immune complex binding and release and the quantitative expression of the complement receptor, type 1 (CR1, CD35) on human erythrocytes.

Primate erythrocytes (E) play a central role in clearing potentially pathogenic immune complexes (IC) from the circulation. E capture circulating IC via interaction between C3b and C4b sites, generated on the IC during activation of the complement cascade, and the complement receptor, type 1 (CR1), expressed on E. IC are released from E when C3b and C4b sites on the IC are cleaved by Factor I. The goal of this study was to examine the interactions between human E and model IC in the context of quantitative variations in CR1 expression. IC were prepared by combining murine monoclonal IgG1, IgG2b, or IgG3 anti-dinitrophenyl (DNP) antibodies with DNP-bovine serum albumin. The expression of CR1 on E, obtained from eight healthy donors, was quantified by radioimmunoassay and Scatchard analysis. On the basis of quantitative CR1 expression, preparations of E obtained from different donors at various times were categorized into phenotypic groups expressing high, intermediate, or low numbers of CR1. While there was some variation in the expression of CR1 of individual donors, five of the eight donors remained within the same phenotypic group upon repeated sampling. Surprisingly, when interactions between IC and E were examined in vitro, there was no direct relationship between the number of CR1 per E and the peak magnitude of IC binding to E. When peak binding and release rates were calculated, there was a direct correlation between the number of CR1 per E and the peak binding rate of IC constructed with IgG3 antibodies (IgG3 IC). In addition, there was an inverse correlation between the number of CR1 per E and the peak release rate of IgG2b IC. There was no direct correlation between the quantitative expression of CR1 on E and the peak binding or release rates of IgG1 IC. These data indicate that the quantitative expression of CR1 can affect the interactions between IC and E, but that these interactions are also dependent upon the immunochemical properties of the IC. These findings may be relevant to the pathogenesis of diseases, including systemic lupus erythematosus and AIDS, in which E express reduced numbers of CR1.