Search

Human G myeloma (7S gamma(2)-myeloma) proteins were investigated for relationships between Gm and Inv genetic factors and the different antigenic types of heavy polypeptide chains (gamma-chains) and light polypeptide chains. Myeloma proteins were isolated from the sera of 1 Chinese, 60 white and 28 Negro individuals. These 89 proteins were tested for eight Gm factors [Gm(a), Gm(x), Gm(b(2)), Gm(f), Gm(b(1)), Gm(b(3)), Gm(b(4)), and Gm(c)], and two Inv factors [Inv(l) and Inv(b)]. Results of the tests were correlated with the four gamma-chain subclasses (gamma(2a), gamma(2b), gamma(2c) and gamma(2d)) and the two types of light polypeptide chains, kappa-chains (type K or I) and lambda-chains (type L or II) found in human IgG molecules. 1. Gm factors were limited to myeloma proteins with heavy polypeptide chains of the gamma(2b)- and gamma(2c)-subclasses. No Gm factors were detected on gamma(2a)- and gamma(2d)-myeloma proteins or on a "heavy-chain" disease protein of subclass gamma(2d). 2. gamma(2b)-Proteins were positive for at least one Gm factor and were either Gm(a+), Gm(a + x+), or Gm(b(2)+ f+). 3. gamma(2c)-Myeloma proteins, and one gamma(2c)-"heavy-chain" disease protein, were positive for at least one Gm factor and contained various combinations of factors Gm(b(1)), (b(2)), (b(4)), and (c). Myeloma proteins from 3 Negroes were included in this group. 4. Inv factors (l) and (b) were limited to myeloma proteins with kappa-light polypeptide chains. These Inv factors were not detected on proteins with lambda-light polypeptide chains. 5. Most (70 per cent) of the gamma(2b)- and gamma(2c)-proteins with kappa-chains were Inv(l+) or Inv(b+). None of the gamma(2a)- or gamma(2d)-proteins with kappa-chains, however, contained these Inv factors.

Analysis of data from 80 families and 369 unrelated individuals confirms the hypothesis that human red cell acid phosphatase phenotypes are determined by three codominant alleles at a single autosomal locus. Further confirmation is afforded by the finding of the predicted sixth phenotype.

Eight nontransfused donors of antibodies against a hereditary gamma-globulin factor lacked the factor, but each donor's mother had it. The probability that this is a chance observation is .00003. A ninth donor had been transfused, and she and her mother both lacked the factor. It is assumed that each nontransfused donor's antibody was formed against his mother's gamma-globulin and that immune tolerance had not been induced.

The relationship between Inv phenotype and the amino acid residue at position 191 in kappa-type light polypeptide chains derived from the immunoglobulins of ten normal human sera was investigated. In each case, the amino acid present at position 191 correlated with the Inv phenotype of the individual. Kappa chains of seven Inv (-1,3) homozygotes had valine, while those of three Inv (1,3) heterozygotes had some chains with leucine and some with valine at this position. Genes encoding the Inv (1) and Inv (3) variants appear to be expressed equally in the heterozygous state, since approximately equal amounts of each gene product was recovered from heterozygotes. The correlation between Inv phenotype and the amino acid residue present at position 191 is identical to that previously established for kappa-type Bence-Jones proteins and myeloma protein light chains. These observations support the hypothesis that the valine-leucine interchange is encoded by two allelic forms of a single kappa-chain common region gene.