TY - JOUR
T1 - Humoral immunostimulation. IV. Role of complement
AU - Shearer, W. T.
AU - Atkinson, J. P.
AU - Frank, M. M.
AU - Parker, C. W.
PY - 1975
Y1 - 1975
N2 - When L cells were treated with anti L cell antibody in medium containing heat inactivated fetal calf serum, nucleoside uptake and cell growth were stimulated. The response was markedly increased when fresh, unheated sera from calves, guinea pigs, humans, mice, or rabbits were also present. The factors in unheated serum responsible for the enhancement of immunostimulation were studied. Using low concentrations of sera deficient in various complement (C) components and low concentrations of antibody, no augmentation of immunostimulation was seen with C1r deficient human serum, C2 deficient human serum, C2, 4 deficient human serum, C4 deficient guinea pig serum, C3 C9 depleted guinea pig serum (by administration of cobra venom factor to animals), but stimulation was observed with C5 deficient human serum, C5 deficient mouse serum and C6 deficient rabbit serum. When the concentration of antiserum was raised, however, augmentation was observed with C4 deficient guipea pig serum. Thus, at low concentrations of antibody, either the classical or alternate C pathways appeared to be involved. Stimulation was specifically restored by puride C2 in C2 deficient serum and by C3 in C3 C9 deficient serum. Under the usual reaction conditions, consumption of guinea pig C component C4 could be demonstrated which provided direct evidence for activation of the classical C pathway under conditions leading to immunostimulation. By immunofluorescence, cells treated with antibody and normal human serum had human C3 deposited at the cell surface. Taken together these observations suggest that C activated through C3 by either the classical or alternate pathways has the potential to enhance nucleoside incorporation into DNA and cell growth of cells exposed to limiting amounts of antibody. Although the mechanism of stimulation is unknown, it is likely to involve a direct effect of C3 at the level of the cell membrane.
AB - When L cells were treated with anti L cell antibody in medium containing heat inactivated fetal calf serum, nucleoside uptake and cell growth were stimulated. The response was markedly increased when fresh, unheated sera from calves, guinea pigs, humans, mice, or rabbits were also present. The factors in unheated serum responsible for the enhancement of immunostimulation were studied. Using low concentrations of sera deficient in various complement (C) components and low concentrations of antibody, no augmentation of immunostimulation was seen with C1r deficient human serum, C2 deficient human serum, C2, 4 deficient human serum, C4 deficient guinea pig serum, C3 C9 depleted guinea pig serum (by administration of cobra venom factor to animals), but stimulation was observed with C5 deficient human serum, C5 deficient mouse serum and C6 deficient rabbit serum. When the concentration of antiserum was raised, however, augmentation was observed with C4 deficient guipea pig serum. Thus, at low concentrations of antibody, either the classical or alternate C pathways appeared to be involved. Stimulation was specifically restored by puride C2 in C2 deficient serum and by C3 in C3 C9 deficient serum. Under the usual reaction conditions, consumption of guinea pig C component C4 could be demonstrated which provided direct evidence for activation of the classical C pathway under conditions leading to immunostimulation. By immunofluorescence, cells treated with antibody and normal human serum had human C3 deposited at the cell surface. Taken together these observations suggest that C activated through C3 by either the classical or alternate pathways has the potential to enhance nucleoside incorporation into DNA and cell growth of cells exposed to limiting amounts of antibody. Although the mechanism of stimulation is unknown, it is likely to involve a direct effect of C3 at the level of the cell membrane.
UR - http://www.scopus.com/inward/record.url?scp=0016669835&partnerID=8YFLogxK
U2 - 10.1084/jem.141.4.736
DO - 10.1084/jem.141.4.736
M3 - Article
C2 - 1168690
AN - SCOPUS:0016669835
VL - 141
SP - 736
EP - 752
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 4
ER -