The authors studied the factors responsible for destruction of cold agglutinin (CA) sensitized erythrocytes (RBC) and examined the role of membrane bound complement components in cell clearance after elution of antibody. Cr51 labeled normal human RBC were sensitized with highly purified IgM CA and incubated in fresh autologous serum under conditions resulting in complement (C) deposition and elution of antibody. Following IV administration, the cells were rapidly cleared by the liver (viz., whole body scanning) in a dose dependent fashion. A proportion were returned to the circulation over several hours and thereafter survived normally. When exposed to C3 inactivator (C3INA) before injection (thereby converting C3b to C3d), the cells survived normally. However, after exposure to CA, C, and C3INA, further exposure to CA and fresh serum did not lead to clearance. Such cells remained immune adherence negative suggesting that there were no available sites for attachment of additional C3b. On the contrary, exposure of the C3 inactivated RBC to IgM anti A isoagglutinin rendered them fully sensitive to C dependent clearance, suggesting different C3b attachment sites with CA and with IgM anti A. When tested in vitro with normal human alveolar macrophage monolayers, rosettes were formed with C3b RBC but not those with C3d fixed. These studies suggest that in vivo sequestration and release of CA sensitized RBC is related to the intrahepatic conversion of C3b to C3d, and protection of CA RBC is afforded by blockage of available sites for further deposition of C3.
|State||Published - Jan 1 1975|