Complement, membrane glycoproteins, and complement receptors: their role in regulation of the immune response.
To determine the effect of complement on the normal antibody response we studied seven patients with genetically determined complement component deficiencies, guinea pigs deficient of C4 and C2, respectively, and two patients whose neutrophils and monocytes lack the C3bi receptor. Patients deficient of early complement components (C4, C2, C3) have abnormal antibody responses to the T-cell-dependent antigen, bacteriophage phi X 174. Complement-deficient guinea pigs (C4, C2) produce less antibody than normal guinea pigs and are unable to maintain measurable antibody levels; during secondary immunization they fail to develop amplification and to switch from IgM to IgG. This defect can be overcome by increasing the antigen dose or by injecting normal guinea pig serum at the time of the primary (but not the secondary) immunization. Patients with deficiency of the C3bi receptor were shown to have a significantly depressed antibody response to T-dependent antigens. We postulate that the contribution of complement to the mature humoral immune response is related to activation of C3. The initial production of IgM following antigen injection leads to antigen-antibody complexes which interact with complement, to be nonspecifically trapped by C3b and C3bi receptors on B cells or macrophages. Thus antigen is selectively accumulated within the lymphoid organs and in turn may entrap antigen-specific B cells by interaction of the trapped antigen with surface immunoglobulin. As a result, close approximation between antigen, antibody, and a network of specific and nonspecific lymphoid cells is initiated, allowing generation of specific memory cells and initiation of a prompt mature antibody response on subsequent exposure to antigen.
D000818:Animals; D000917:Antibody Formation; D003165:Complement System Proteins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D006023:Glycoproteins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D011951:Receptors, Complement / Q000235:genetics / Q000502:physiology*; D017463:Receptors, Complement 3b
D006023:Glycoproteins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D003165:Complement System Proteins