MOLECULAR CHARACTERIZATION OF IMMUNOGLOBULIN G4 GENE ISOALLOTYPES

The molecular bases of classical serological immunoglobulin allotypes are progressively uncovered through detailed characterization of the r elevant genes. Here we describe two isoallotypic determinants of the G 4 gene. In the first, Leu 309, as in G1 and G3, is changed to Val, as in G2; studies on myeloma proteins have long assigned the immunologica lly defined nG4 m(a)/(b) to the same position. The two molecular varia nts, here called IGHG4L309 and IGHG4*V309, are allelic in IGHC haplot ypes with a single G4 gene, but can be found together in cis in G4-dup licated haplotypes. A second isoallotypic variant was found at codon 4 09, where either Arg, as in G1 and G3, or Lys, as in G2, can be found. Both isoallotypes are associated with several 'silent isoallotypic' s ubstitutions dispersed through the hinge, CH2 and CH3 domains. This su ggests segmental gene conversion as the common mechanism of origin.