In vivo and in vitro binding of C4 molecules on red cells: a correlation of numbers of molecules and agglutination.
The fourth component of human complement (C4) is one that is essential to the antibody-mediated classical activation pathway. C4d, present on all normal and most patient red cells (RBCs), may be detected by the human antisera anti-Rodgers (Rg) and -Chido (Ch). A study has been made of the Rg/Ch antigens on normal and patient RBCs in an attempt to understand the mechanism by which C4 is bound to normal RBCs in the absence of RBC antibodies (Abs). Because RBCs from C1q-deficient patients express Rg/Ch, it seems that C1q is not essential for C4 binding. Treatment of normal RBCs with proteolytic enzymes, including trypsin, eliminated positive reactions with anti-Rg/Ch even though the C4d fragment is considered to be resistant to cleavage by trypsin. By correlating agglutination reactions with numbers of bound C4d and C3d molecules, it is evident that both C4d and C3d were affected by trypsin treatment and that anti-Rg/Ch were not capable of agglutinating RBCs with less than 50 molecules of bound C4d. It is concluded that trypsin-sensitive and -insensitive RBC membrane structures may both act as acceptors for C4. RBCs with null phenotypes of the major blood group systems all expressed Rg/Ch antigens, so none of the structures that carry these antigens act preferentially as acceptors for C4.
Giles
C M
CM
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Davies
K A
KA
Walport
M J
MJ
D000372:Agglutination Tests; D000906:Antibodies; D000911:Antibodies, Monoclonal; D003176:Complement C3 / Q000032:analysis / Q000378:metabolism; D003181:Complement C4 / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D015935:Complement C4b; D000939:Epitopes; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology; D011869:Radioligand Assay
D000906:Antibodies; D000911:Antibodies, Monoclonal; D003176:Complement C3; D003181:Complement C4; D000939:Epitopes; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d