The regulation of IgG subclass production in man: low serum IgG4 in inherited deficiencies of the classical pathway of C3 activation

摘要

AbstractHuman serum IgG subclasses have been measured by a sensitive enzyme‐linked immunoassay in 52 subjects with severe genetic deficiency of a complement component. The mean serum IgG4in 4 subjects with C3 deficiency was 8.2 γg/ml and in 14 subjects with (C1‐4 deficiency was 27.9 γg/ml. These means are severely depressed compared with the mean normal IgG4 of 292 γg/ml. IgG4 levels in C5‐9 deficiency (175 γg/ml) and ClINH deficiency (179 γg/ml) did not differ significantly from normal. Serum IgG2was reduced significantly, but far less severely than IgG4, in C3 and in some cases of C1‐4 deficiency. IgGland IgG3levels were within the normal range in all complement‐deficient groups. Age differences between the groups do not explain the very low levels of IgG4 in C1‐4 and C3 deficiency. These data suggest that serum IgG4 synthesis is dependent on an intact classical, but not alternative, pathway for activation of C3 and that IgGCcommitted B cells require a complement‐dependent maturation pathway not required by B cells committed to other IgG isotypes. IgG4antibody responses are associated with secondary responses to T‐dependent antigens. The possibility that IgG4may be the product of a memory B cell which has been through a stage of differentiation in a germinal