Elevated NK sensitivity of Raji cells carrying acceptor-bound C3 fragments.
The majority of cell lines derived from Burkitt lymphomas carry CR2 on their plasma membrane cell lines of haematopoietic origin can activate C3 present in human serum through the alternative pathway. However, only the lines that carry CR2 were shown to bind C3 fragments. This bond can be either fixation to acceptor sites or attachment to the CR. Our studies with Raji cells showed that when the possibility for the covalent acceptor bond was eliminated by using methylamine (MA)- or zymosan-treated serum, considerably lower amounts of C3 were bound. In the zymosan-treated serum C3 fragments are present that can bind to receptors but their capacity for acceptor bond is absent. These results indicate that when Raji cell are incubated in human serum some of the generated C3 fragments are bound to acceptors and a lower proportion through the specific interaction with complement receptors. Pretreatment of the CR2 carrying cell lines with human serum elevated their sensitivity to the lytic effect of human blood lymphocytes. We showed in this work that MA-treated serum did not induce this elevation. Zymosan-treated serum under conditions that excluded activation of the residual native C3 molecules, i.e., in the presence of EDTA, did not have the enhancing effect either. These results suggest that the increased lytic efficiency imposed by human serum was due to cleavage of C3 molecules by Raji and fixation of the C3 fragments by acceptor sites. Natural killer cells carry CR3; therefore it is likely that the attached C3 fragments bind also to the effector cells. The C3 molecules could elevate thereby the avidity between the target and the lytic lymphocytes. The observation that C3 fragments are not bound to the surface of CR2 negative lines in spite of their capacity to activate C3 suggests that the receptor molecule is either involved in the activation and/or serves also as an acceptor.
Kai
C
C
Department of Tumor Biology, Karolinska Instituet, Stockholm, Sweden.
Sármay
G
G
Ramos
O
O
Yefenof
E
E
Klein
E
E
D003176:Complement C3 / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D008744:Methylamines / Q000494:pharmacology; D011951:Receptors, Complement / Q000502:physiology; D014407:Tumor Cells, Cultured; D015054:Zymosan / Q000494:pharmacology
D003176:Complement C3; D008744:Methylamines; D011951:Receptors, Complement; D015054:Zymosan; C027451:methylamine