Distinctive role of IgG1 and IgG3 isotypes in Fc gamma R-mediated functions.
Polyclonal and monoclonal anti-Rh (D) antibodies of IgG1 and IgG3 subclass were evaluated for their capacity to sensitize erythrocytes and (i) to trigger monocyte and K-cell mediated antibody-dependent cellular cytotoxicity (ADCC); (ii) to mediate binding to monocyte and lymphocyte Fc gamma R; (iii) to stimulate phagocytosis by monocytes. All antibodies were equally effective in mediating monocyte or activated U937 cell ADCC but IgG1 was more active than IgG3 in K-cell mediated ADCC. IgG3-sensitized erythrocytes inhibited IgG1-induced lysis, suggesting that each subclass engages the same Fc gamma R receptor but that lysis requires a further 'signal' that the IgG3 molecule can not deliver. Two monoclonal IgG3 anti-D antibodies were shown to have higher binding (two times) and phagocytic (three times) indices than IgG1 antibody for monocytes; similar differences were observed for polyclonal IgG1 and IgG3 antibodies. The same pattern was observed in an EA rosette assay when a total lymphocyte population was used; however, this difference was not seen with a B-cell depleted (T+ null cell) lymphocyte population.
Rozsnyay
Z
Z
Department of Immunology, L. Eötvös University, Göd, Hungary.
Sármay
G
G
Walker
M
M
Maslanka
K
K
Valasek
Z
Z
Jefferis
R
R
Gergely
J
J
D000911:Antibodies, Monoclonal / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D000943:Antigens, Differentiation / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D010587:Phagocytosis; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG; D012204:Rh-Hr Blood-Group System / Q000276:immunology; D012397:Rosette Formation
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D012204:Rh-Hr Blood-Group System