Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2.
Complement receptor 1 (CR1, CD35) and complement receptor 2 (CR2, CD21) have been implicated as regulators of B-cell activation. We explored the role of these receptors in the development of humoral immunity by generating CR1- and CR2-deficient mice using gene-targeting techniques. These mice have normal basal levels of IgM and of IgG isotypes. B- and T-cell development are overtly normal. Nevertheless, B-cell responses to low and high doses of a T-cell-dependent antigen are impaired with decreased titers of antigen-specific IgM and IgG isotypes. This defect is not complete because there is still partial activation of B lymphocytes during the primary immune response, with generation of splenic germinal centers and a detectable, although reduced, secondary antibody response. These data suggest that certain T-dependent antigens manifest an absolute dependence on complement receptors for the initiation of a normally robust immune response.
Molina
H
H
Department of Internal Medicine and Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Holers
V M
VM
Li
B
B
Fung
Y
Y
Mariathasan
S
S
Goellner
J
J
Strauss-Schoenberger
J
J
Karr
R W
RW
Chaplin
D D
DD
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D018390:Gene Targeting; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000145:classification; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D017463:Receptors, Complement 3b / Q000172:deficiency* / Q000235:genetics; D017464:Receptors, Complement 3d / Q000172:deficiency* / Q000235:genetics; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d