QUANTITATIVE STUDIES OF Gm ALLOTYPES:V. SIMULTANEOUS PRESENCE OF LATENT Gm ALLOTYPES AND DEFICIENT Gm GENES IN A FAMILY WITH HYPOGAMMAGLOBULINAEMIC PROBANDS

Salier, Jean‐Philippe; Rivat, L; Daveau, Maryvonne; Lefranc, G.; Breton, Pascal; deMenibus, C. H.; Henocq, A; Fudenberg, H. Hugh

doi:10.1111/j.1744-313x.1980.tb00714.x

Cited by 9 publications

(8 citation statements)

References 36 publications

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“…1), in disease association and linkage analyses, in forensic medicine, and in fundamental studies of the evolution of the heavy chain constant region (CH) genes (Steinberg 1973, van Loghem et al 1980, 1982, G. Lefranc et al 1976, 1978, 1979a, b, 1982, Huck et al 1986a, Lefranc and Lefranc, 1987. Extensive serological studies have revealed unusual Gm haplotypes characterized by the excess, lack, or exchange of allotypes (G. Lefranc et al 1976, 1978, 1979a, b, 1982, Salier et al 1980, van Loghem et al 1980, 1982, and it has been proposed that most of these uncommon haplotypes could be explained by gene conversion events (M.-P. Lefranc et al 1986a).…”

Section: Introductionmentioning

confidence: 96%

A human immunoglobulinIGHG3 allele (Gmb0, b1, c3, c5, u) with anIGHG4 converted region and three hinge exons

Huck

Lefranc

1989

Immunogenetics

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The five human IGHG genes consist of three constant domain exons plus one of or four hinge exon(s), the quadruplicated hinge region being characteristic of the IGHG3 gene. Besides this structural difference, the IGHG genes are polymorphic, as demonstrated by the restriction fragment length polymorphism and, at the protein level, by the Gm allotypic antigenic determinants. In this paper, we report the sequence of the G3m(b0, b1, c3, c5,u) IGHG3 allele, typical of the Black African populations and of populations with Negroid admixture, found in a homozygous Tunisian designated as LAT. We demonstrate that this G3 allele contains only three hinge exons instead of four (the probable result of an unequal crossing over) and that IGHG3 genes with triplicated hinge exons (and therefore encoding shorter gamma 3 chains) are present in healthy individuals from different populations. Moreover, we show that the LAT G3m (b0, b1, c3, c5, u) coding sequence results from the conversion, in the CH3 exon, of the G3m (b0, b1, b3, b4, b5, u, v) allele, the most frequent IGHG3 gene in the Negroid populations, by the homologous region of a IGHG4 gene. The structural features of the LAT IGHG3 allele, which are the lack of one hinge exon and its conversion by the IGHG4 gene, demonstrate that both crossing-over and gene conversion events occur in the evolution of the human IGHG genes.

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Section: Introductionmentioning

confidence: 96%

A human immunoglobulinIGHG3 allele (Gmb0, b1, c3, c5, u) with anIGHG4 converted region and three hinge exons

Huck

Lefranc

1989

Immunogenetics

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“…as a haplotype, as are the Gm3 and Gm5 genes. Caucasians are thus either Gtn';2'/Gm';21 or Gm3;s/Gm3;3 or heterozygous Gm';21/Gm3;s. Occurrence of latent G m allotypes has been reported in peripheral blood lymphocyte cultures (Lobb et al, 1967;Rivat el al., 1970Rivat el al., , 1973 and has been proposed as an explanation of qualitative or quantitative abnormalities in family studies (Lefranc et al, 1977;Rivat et al, 1977;Blanc et al, 1980;Salier et al, 1980). However, in most of these studies, allotypic determinants were measured using haemagglutination inhibition, a technique not quantitatively precise.…”

Section: Introductionmentioning

confidence: 99%

LATENT IMMUNOGLOBULIN G (Gm) ALLOTYPES: OCCURRENCE IN THE CEREBROSPINAL FLUID IN SOME NEUROPATHOLOGICAL STATES

Salier

Link

et al. 1983

Int J Immunogenetics

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SUMMARY Gm allotypes were detected and quantitated by radioimmunoassay (RIA) in paired serum and CSF samples from patients suffering from various neurological diseases. Of 115 patients with neurological disorders (65 MS and 50 others), seven subjects displayed one or two allotypes in their CSF which were absent in serum. The Gm phenotype in the patient's serum allowed us to infer the genotype without the need of familial data. A comparison of the regression curves obtained in RIA from the unexpected allotype in CSF and the counterpart in a normal serum pool argued for an identity of the Gm antigen carried by both inhibitory molecules. The unexpected allotype(s) in CSF can be considered as the product of a latent Gm gene which may be activated by either immune perturbations due to the disease per se or some particular immune regulations in the central nervous system.

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“…Furthermore, except in a few cases (12,13), the characteristics of these reagents dictate their use in a hemagglutination-inhibition typing assay that depends on visual scoring and requires additional sources of human cells and "target" Rh antisera from a variety of donors (1).…”

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confidence: 99%

“…Thus, a whole series of genetic markers have been inaccessible for lack of an appropriate assay system. Past attempts to develop radioimmunoassays (RIAs) have met with only variable success, primarily due to problems in purifying and radiolabeling antibodies from conventional antisera (12,13). The mouse monoclonal anti-Gm typing reagents and RIA typing methods described here signal an end to these difficulties.…”

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confidence: 99%

Human immunoglobulin allotypes: previously unrecognized determinants and alleles defined with monoclonal antibodies.

Zelaschi¹,

Newby²,

Parsons³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

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The highly polymorphic system of serologically defined genetic markers on human IgG heavy chains (Gm allotypes) is second only to the HLA complex in terms of the large number of determinants, alleles, and haplotypes that can be used for analyses of disease associations and other genetic studies. However, present typing methods are based on the use of antiGm antisera that are derived mainly from fortuitously immunized human donors, often requiring processing before use, and must be used in a hemagglutination-inhibition assay that cannot be used in typing for isoallotypic determinants (currently termed "nonmarkers"). In studies presented here, we describe an allotyping system that utilizes monoclonal antibodies in a "sandwich" modification of the solid-phase radioimmunoassay, which is capable of reliable quantitative typing of allotypic, isoallotypic, and isotypic immunoglobulin determinants. We show that these highly reproducible, easily disseminated, and essentially inexhaustible reagents can be used for rapid, sensitive, and quantitative Gm typing. Using this system we define two previously unrecognized Gm determinants, one of which, found to date only in Caucasians, is different from all known Gm markers and thus defines previously unrecognized alleles and haplotypes. The other determinant cosegregates with the conventional G3m(bl) marker but is distinct from that marker on serological grounds. The successful preparation of mouse monoclonal antibodies that detect human Gm allotypic differences and the development of an assay system capable of typing isoallotypic as well as allotypic determinants opens the way to further dissection and application of this rich genetic system.

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QUANTITATIVE STUDIES OF Gm ALLOTYPES:V. SIMULTANEOUS PRESENCE OF LATENT Gm ALLOTYPES AND DEFICIENT Gm GENES IN A FAMILY WITH HYPOGAMMAGLOBULINAEMIC PROBANDS

Cited by 9 publications

References 36 publications

A human immunoglobulinIGHG3 allele (Gmb0, b1, c3, c5, u) with anIGHG4 converted region and three hinge exons

A human immunoglobulinIGHG3 allele (Gmb0, b1, c3, c5, u) with anIGHG4 converted region and three hinge exons

LATENT IMMUNOGLOBULIN G (Gm) ALLOTYPES: OCCURRENCE IN THE CEREBROSPINAL FLUID IN SOME NEUROPATHOLOGICAL STATES

Human immunoglobulin allotypes: previously unrecognized determinants and alleles defined with monoclonal antibodies.

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