STRUCTURAL AND IMMUNOLOGICAL ANALYSIS OF GENE TRIPLICATIONS IN THE IGHEAVY-CHAIN CONSTANT-REGION LOCUS

The Ig H chain C region is a multigene family often involved in genomi c rearrangements leading to deleted and duplicated haplotypes, most pr obably through unequal crossing over between homologous regions within the locus. The frequency of these haplotypes in Italy is around 2.7% each. Using PFGE analysis in two unrelated Italian families we found a n abnormal high m.w. band, inherited in a Mendelian fashion. To assess the extension of the haplotype we performed Southern blot analysis us ing several specific Ig H chain C probes. In both cases, the haplotype turned out to be triplicated, with three copies of the genes from A1 to E. In one family segregation of a duplication from EP to G4 was als o observed. Analysis of polymorphic loci suggests that the two triplic ations are of independent origin. Serological detection of IgA2 alloty pes demonstrated the functional activity of the genes at the 3' end of the triplicated locus, ruling out any major effect of these large gen omic rearrangements on Ig class switching. Furthermore, the triplicate d haplotype does not seem to give rise to any clinically significant i mmunological impairment or increase in Ig serum concentrations.