Linkage of total deficiency of the second component (C2) of the complement system and of genetic C2-polymorphism to the major histocompatibility complex of the guinea pig.

Abstract

Abstract In the guinea pig six common phenotypes for hemolytically active C2 were detected. They resulted from three allotypic variants: a basic C2B and two more acidic variants C2A and C2A1. (The gene frequency for C2B in the outbred population was 0.36, 0.33 for C2A, and 0.31 for C2A1.) These variants were inherited as autosomal codominant traits. A strong linkage-disequilibrium between C2 and C4 allotypes was observed consisting of the pairs C2A1-C4F. C2A-C4S, whereas C2B was associated with either C4S or C4S1. To investigate the linkage of C2 to the MHC a family of strain 2 X strain OM3 was studied: the C2B allotype segregated with the strain haplotype of OM3 whereas C2A1 does the same with the strain 2 haplotype. During the C2-typing, an animal totally deficient in hemolytic C2 activity was discovered. Its C1, C4, C3, C5, factors B, D, and H were normal. Breeding yielded finally homozygous and heterozygous-deficient individuals. The latter ones exhibited 50 to 60% of the hemolytic activity of normal guinea pigs. Combined typing data of C4, C2 and GPLA showed that the deficient gene behaved like a rare, silent allele of C2, which is GPLA-linked and inherited like the normal C2-variants. An antiserum against C2 was raised in C2-deficient animals, which reacted with normal guinea pig serum but not with serum from C2-deficient animals. No cross-reactivity with human or mouse serum could be detected.