Antibody production in mice deficient for complement receptors 1 and 2 can be induced by IgG/Ag and IgE/Ag, but not IgM/Ag complexes.
Deficiencies in C factors C2, C3, or C4 as well as lack of C receptors 1 and 2 (CR1/2) lead to impaired Ab production. Classical pathway activation plays a major role, as mice deficient in factor B, a key factor in the alternative pathway, have normal Ab production. Abs in complex with their specific Ag are known to feedback regulate the Ab response, and enhanced responses are initiated by IgM, IgE, and IgG. IgM acts via the C system, whereas IgE and IgG can operate independently of C via Fc receptors. Here we have investigated whether these isotypes are able to enhance Ab responses in mice lacking CR1/2. SRBC-specific IgM, administered with SRBC, does not enhance Ab responses in these animals. In contrast, 2,4, 6-trinitrophenyl-specific IgE and IgG2a, administered with BSA-2,4, 6-trinitrophenyl, induce potent Ab responses in CR1/2-deficient mice. Additionally, BSA administered with CFA or alum induced strong Ab responses in the absence of CR1/2. These results indicate that CR1/2 is needed to promote IgM-mediated induction of primary Ab responses. The data also show that the need for CR1/2 can be circumvented by Abs typical of a secondary immune response forming complexes with Ag or by conventional adjuvants, presumably mimicking physiological inflammatory reactions.
Applequist
S E
SE
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Dahlström
J
J
Jiang
N
N
Molina
H
H
Heyman
B
B
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000936:Antigen-Antibody Complex / Q000008:administration & dosage*; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D006462:Hemolytic Plaque Technique; D007073:Immunoglobulin E / Q000008:administration & dosage; D007074:Immunoglobulin G / Q000008:administration & dosage; D007075:Immunoglobulin M / Q000008:administration & dosage; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000235:genetics*; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D017463:Receptors, Complement 3b / Q000172:deficiency* / Q000235:genetics*; D017464:Receptors, Complement 3d / Q000172:deficiency* / Q000235:genetics*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D000936:Antigen-Antibody Complex; D000941:Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; C038601:trinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E; D010047:Ovalbumin