Immunoglobulin Genomics in the Guinea Pig (Cavia porcellus)

In science, the guinea pig is known as one of the gold standards for modeling human disease. It is especially important as a molecular and cellular biology model for studying the human immune system, as its immunological genes are more similar to human genes than are those of mice. The utility of the guinea pig as a model organism can be further enhanced by further characterization of the genes encoding components of the immune system. Here, we report the genomic organization of the guinea pig immunoglobulin (Ig) heavy and light chain genes. The guinea pig IgH locus is located in genomic scaffolds 54 and 75, and spans approximately 6,480 kb. 507 VH segments (94 potentially functional genes and 413 pseudogenes), 41 DH segments, six JH segments, four constant region genes (μ, γ, ε, and α), and one reverse δ remnant fragment were identified within the two scaffolds. Many VH pseudogenes were found within the guinea pig, and likely constituted a potential donor pool for gene conversion during evolution. The Igκ locus mapped to a 4,029 kb region of scaffold 37 and 24 is composed of 349 Vκ (111 potentially functional genes and 238 pseudogenes), three Jκ and one Cκ genes. The Igλ locus spans 1,642 kb in scaffold 4 and consists of 142 Vλ (58 potentially functional genes and 84 pseudogenes) and 11 Jλ -Cλ clusters. Phylogenetic analysis suggested the guinea pig’s large germline VH gene segments appear to form limited gene families. Therefore, this species may generate antibody diversity via a gene conversion-like mechanism associated with its pseudogene reserves

Gene segments encoding membrane domains of the human immunoglobulin gamma 3 and alpha chains.

International audienceThe carboxyterminal region of the heavy chains, according to its hydrophilic or hydrophobic properties, determines whether the immunoglobulin will be secreted or membrane-bound. We have determined the nucleotide sequences of the human IGHG3, IGHA1, and IGHA2 membrane exons isolated from genomic DNA libraries. The IGHG3 M1 and M2 exons are separated by a long intron of 2.1 kilobases (kb) containing an highly repeated motif of 34 base pairs (bp). The IGHA1 and IGHA2 genes, like the mouse Igh-A gene, have a single exon encoding the extracellular, transmembrane, and cytoplasmic regions. For each class of immunoglobulins, the sequences of membrane exons are highly conserved between human and mouse, but no alignment is possible for the flanking regions. In contrast, for a same species, the sequences of the heavy chain membrane exons differ from one class to another. While the hydrophobic profile of the membrane core is well conserved, the cytoplasmic region differs in length and in composition. None of the intracellular domains presents the sequence implied in signal transduction, implying that membrane immunoglobulins need other proteins, which probably interact with the constant or membrane domain, to transmit signals leading to B-cell activation

Localization of the human T-cell receptor gamma locus (TCRG) to 7p14→p15 by in situ hybridization

International audienceThe human T cell receptor gamma locus (TCRG) has previously been localized on chromosome 7 at band 7p15. In situ hybridization of a TCRG-specific probe allowed us to map the locus at 7p14----p15. These data confirm the previous localization and are in agreement with the molecular characterization of an inversion of chromosome 7, inv(7) (p14q35) which involves the TCRG locus

Sequence of the CHI and hinge-CH2 exons of the human immunoglobulin IGHA2 A2m(2) allele: comparison with the nonallelic and allelic IGHA genes

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The human immunoglobulin pseudo-gamma IGHGP gene shows no major structural defect.

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The immunoglobulin lambda-like gene cluster (14.1, 16.1 and F lambda 1) contains gene(s) selectively expressed in pre-B cells and is the human counterpart of the mouse lambda 5 gene.

International audienceA human immunoglobulin (Ig)-related gene, covering approximately 8 kb, was isolated from a cosmid genomic library, by hybridization with a C lambda probe and with a lambda-like probe. This gene was identified as 14.1 It belongs to the human lambda-like cluster which is composed of three genes (14.1, 16.1 and F lambda 1) that do not rearrange. Sequence data indicate that 14.1 is organized similarly to the mouse lambda 5 gene. It contains three exons with lengths of 69, 38, and 106 codons as compared with 65, 38, and 106 for exons 1, 2, and 3 of mouse lambda 5, respectively. The corresponding homology values were 61, 66 and 75.5%. Using a 14.1 specific probe containing exon 1, we showed that this gene was selectively expressed in human pre-B cell lines. It is likely to encode a 213-amino acid lambda-like light chain that would associate with mu chains and play an important role in the early steps of B cell differentiation

BamHI and SacI RFLPs of the human immunoglobulin IGHG genes with reference to the Gm polymorphism in African people. Evidence for a major polymorphism.

International audienceIn this paper, we extend the study of the IGHG gene RFLPs in black African persons and in some other individuals characterized by a Negroid admixture. We demonstrate a polymorphism that is much more important in black Africans, than in Caucasoids, mainly for the IGHG3 and G1 genes, the most 5' members of the IGHG multigene family. These genes encode for the IgG3 and IgG1 subclasses, which are of crucial biological importance

RFLP detected by the transmembrane exon probe of the human immunoglobulin IGHA genes

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Polymorphism of immunoglobulin lambda constant region genes in populations from France, Lebanon and Tunisia.

International audiencePolymorphism of immunoglobulin lambda constant region (IGLC) genes has been studied in French, Lebanese and Tunisian people. The human IGLC polymorphisms appear as EcoRI restriction fragment length variations-8, 13, 18 or 23 kb-, these polymorphic fragments being related to a number of IGLC genes varying from six to nine per haploid genome. DNAs digested with the endonucleases EcoRI and HindIII were hybridized to a human IGLC probe and an immunoglobulin lambda intervening sequence region probe containing the J lambda 2 gene segment. Restriction fragments detected in Southern hybridizations were assigned to the IGLC locus map. Family studies allowed us to confirm the allelic nature of four of the different EcoRI restriction fragments observed. Frequencies of the corresponding alleles in French, Lebanese and Tunisian populations were determined and compared. The decrease of the 8-kb fragment (allele A1) frequency and, conversely, the increase of that of the 13-kb and 18-kb fragments (alleles A2 and A3) seemed to be correlated to a Negroid African contribution in the gene pool more important in Tunisia than in Lebanon

Restriction fragment haplotypes in the human immunoglobulin IGHG locus and their correlation with the Gm polymorphism

International audienceOf the four human IgG subclass heavy chain (IGHG) genes, three--IGHG1, IGHG2 and IGHG3--have allelic forms which encode antigenic determinants called G1m, G2m and G3m allotypes for markers of the IgG1, IgG2 and IgG3 molecules. The alleles at these three closely linked loci are transmitted as Gm haplotypes, together with the IGHG4 and the IGHGP (or pseudo gamma) genes. Restriction Fragment Length Polymorphisms (RFLPs) have been described for all these IGHG genes, allowing us to define at least 15 RFLP alleles (N. Ghanem et al., Eur. J. Immunol. 1988. 18:1059). In this article, we determine unambiguously the Gm alleles and haplotypes and the associated RFLPs in French, Lebanese and Tunisian families, chosen for the various Gm phenotypes of their members, in order to correlate both these polymorphisms and to know the evolution of the IGHG multigene family. We were able to assign all the IGHG alleles to the Gm alleles and to their linked IGHG4 and IGHGP genes allowing us to define restriction fragment haplotypes of the IGHG gene family