Mutant monoclonal antibodies with select alteration in complement activation ability. Impact on immune complex functions in vivo.
Mutagenesis of mAb is a useful means for studying the biologic and pathologic functions of immune complexes. Treatment of the Hy-1.2 hybridoma-producing IgG2a-anti-TNP antibodies with ethylmethanesulfonate provided us with a mutant clone, producing antibodies with reduced capacity for C activation. The antibodies retained normal Ag-binding capacity, staphylococcal protein A reactivity, and association to FcR for IgG on murine macrophages. No significant polypeptide deletion or class-switch was observed, but a significant change in clonotype was revealed by IEF. Intravenous injection of the mutant antibodies in immune complex form induced different tissue distributions of Ag in mice; i.e., more in kidneys and less in spleen, and developed more mesangial deposits in renal glomeruli compared with those of the wild type. Moreover, the production of granulomatous lesions in vivo caused by immune complexes of TNP-Sepharose was augmented by using mutant antibodies. These lesions demonstrated an enhanced accumulation of macrophages with multinucleated giant cells. Availability of this kind of mutant mAb is thus helpful in the elucidation of the biologic functions and consequences of immune complexes.
Nose
M
M
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
Okuda
T
T
Gidlund
M
M
Ramstedt
U
U
Okada
N
N
Okada
H
H
Heyman
B
B
Kyogoku
M
M
Wigzell
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000235:genetics / Q000302:isolation & purification; D000920:Antibody-Dependent Cell Cytotoxicity; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001666:Binding Sites, Antibody; D003167:Complement Activation; D003170:Complement Pathway, Alternative; D006099:Granuloma / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000235:genetics / Q000302:isolation & purification; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009153:Mutagens; D011961:Receptors, Fc / Q000378:metabolism; D013205:Staphylococcal Protein A / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D009153:Mutagens; D011961:Receptors, Fc; D013205:Staphylococcal Protein A