[Polymorphism of factor B of the properdin system (C3PA, GBG, and Bf) and histocompatibility-complement linkage]

Several recent studies have shown that the genetic polymorphism of factor B of the Properdin system (GBG or Bf) is closely linked to the major histocompatibility complex (MHC). The genetic polymorphism of Bf, a component of the alternate pathway of complement activation, is revealed by "immunofixation" technique after prolonged high voltage agarose electrophoresis. In this report, we describe technique for the Bf grouping and give the results in two families showing the linkage between HL-A and Bf loci. The study of a family with a recombinant between the second HL-A locus (SD-2) and the major MLC locus (LD-1) provides evidence that the Bf locus is not located outside the MLC's because the Bf allele remains linked to the SD-2 allele. In this family, a crossover occurs between Bf and LD-1, and since crossovers between Bf and SD-2 have already been discovered, it is now possible to locate the Bf locus between SD-2 and LD-1. The Bf phenotypes were determined in the serum of 247 normal unrelated caucasian individuals from the area of Strasbourg. The calculated allele frequencies in this population are: BfS=0.757, BfF=0.219, BfS1=0.014, BfF1=0.010. These allele frequencies are intermediary between those found by ALPER and RITTNER. The linkage between MHC and the complement system is now even more evident after the discovery that genes involved in the synthesis of the second and fourth complement components also belong to the MHC on the chromosome 6. These linkages were demonstrated by the study of several families with hereditary C2 deficiency in the U.S.A., and one family with C4 deficiency discovered in Strasbourg. C2 deficiency was found to be associated with three kinds of HL-A haplotypes (HL-A 10, W18; HL-A 2, W18 and HL-A2, 4A2) and the LD-7a specificity. In the family with C4 deficiency, the C4 deficient gene is associated with the HL-A haplotype 2, T3, W10 and a new hitherto unknown MLC type "Re". The linkage between C4 and MHC has been demonstrated recently also in the mouse (the Ss protein in the complement C4 fraction in the mouse) and in the guinea pig. The significance of the genetic linkage between some important components of the complement system and MHC is still unknown. It appears necessary to study all the genetic markers located within or in the vicinity of the MHC region on the chromosome 6 in investigations of the relationship between "pathologic states and HL-A antigens".