Complement-activating ability of leucocytes from patients with complement factor I deficiency.
Previous studies from this laboratory have shown that normal peripheral blood B cells are capable of activating complement via the alternative pathway (AP), that the activation is associated with complement receptor type 2 (CR2) expression, and that erythrocytes at normal blood levels partially inhibit the activation. The purpose of the present study was to investigate whether factor I (FI) deficiency, which leads to continued formation of the AP convertase (C3bBb) resulting in the consumption of factor B and C3 and large scale generation of C3b fragments, affects the phenotype and/or function of the patients' B cells. Using flow cytometry, peripheral blood leucocytes (PBL) from two FI-deficient patients were investigated for expression of complement receptors and complement regulatory proteins, in vivo-deposited C3 fragments and in vitro complement-activating ability. CR1 levels on B cells were significantly lower in FI-deficient patients than in normal individuals, whereas CR2 levels were found to be reduced, although not to a significant extent. CR1 levels on monocytes and polymorphonuclear leucocytes (PMN) were found to be normal or slightly raised. All leucocyte subpopulations were found to be covered in vivo with C3b fragments. AP activation on B cells from FI-deficient patients in homologous serum was significantly reduced compared with that for normal individuals, whereas no in vitro activation was seen in autologous serum. In addition, the in vivo-bound C3b fragments were degraded to C3d,g when the patients' PBL were incubated in homologous serum containing EDTA. Finally, the patients, erythrocytes failed to exert any inhibition on AP activation in homologous serum.
Marquart
H V
HV
Department of Medical Microbiology, Odense University, Denmark.
Rasmussen
J M
JM
Leslie
R G
RG
D015703:Antigens, CD / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D018958:CD55 Antigens / Q000097:blood; D002450:Cell Communication / Q000276:immunology; D018929:Cell Culture Techniques; D003176:Complement C3 / Q000378:metabolism; D017244:Complement Factor I / Q000172:deficiency*; D003170:Complement Pathway, Alternative / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000097:blood; D011951:Receptors, Complement / Q000097:blood
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D003176:Complement C3; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; D017244:Complement Factor I