Functional properties of membrane-associated complement receptor CR1.
It was previously shown that membrane receptors for C3b (CR1) purified from human erythrocytes were powerful inhibitors of the complement cascade and that they encompass the regulatory functions of the serum proteins beta 1H (H) and C4-binding protein (C4bp). In the present report we study the functional properties of membrane-associated CR1. When tonsil lymphocytes, which contain between 30 and 60% of CR1-bearing B cells, are incubated with the red cell complement intermediate EAC14oxy2lim or EAC14oxy23lim, they inhibit both C42 and C423 in a dose-dependent manner. These effects are mediated by membrane-associated molecules. Indeed, mild trypsinization of the lymphocytes abolishes their activity, and formaldehyde-fixed cells are as effective as viable cells. The inhibitory effects are in part mediated by CR1. The lymphocyte activities are reversed about 60% if monoclonal antibodies to CR1 or fluid phase C3b are present in the incubation medium. Moreover, upon addition of C3b-inactivator (l), lymphocytes release C3c fragments from EAC14oxy23b. The release of C3c was also abolished by antibodies to CR1. These results support the idea that CR1, as well as other molecules from the lymphocyte membrane, can function as inhibitor(s) of complement activation in their vicinity.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism / Q000502:physiology; D015932:Complement C3c; D003169:Complement Inactivator Proteins / Q000032:analysis; D005557:Formaldehyde / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D014066:Palatine Tonsil / Q000166:cytology*; D011951:Receptors, Complement / Q000276:immunology / Q000502:physiology*; D017463:Receptors, Complement 3b
D000911:Antibodies, Monoclonal; D003176:Complement C3; D003169:Complement Inactivator Proteins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D005557:Formaldehyde; D003179:Complement C3b; D015932:Complement C3c