Structure of the genomic sequence comprising the immunoglobulin heavy constant (IGHC) genes from Sus scrofa

Eguchi-Ogawa, Tomoko; Toki, Daisuke; Wertz, Nancy; Butler, John E.; Uenishi, Hirohide

doi:10.1016/j.molimm.2012.05.010

Cited by 26 publications

(25 citation statements)

References 52 publications

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“…Convincing evidence could be best obtained by studying the Cγ subclasses of other swine related species that are related to the ancestors of the domesticated pig. Consistent with studies on human Cγ (LeFranc et al, 1991), there is also evidence for deletion of some Cγ genes in some pigs (Butler and Wertz, 2006; Eguchi-Ogawa et al, 2012). …”

Section: Antibody Repertoire Development and The Origin Of The Genomisupporting

confidence: 69%

The Porcine Antibody Repertoire: Variations on the Textbook Theme

Butler¹,

Wertz²

2012

Front. Immun.

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The genes encoding the heavy and light chains of swine antibodies are organized in the same manner as in other eutherian mammals. There are ∼30 VH genes, two functional DH genes and one functional JH gene, 14–60 Vκ genes, 5 Jκ segments, 12–13 functional Vλ genes, and two functional Jλ genes. The heavy chain constant regions encode the same repertoire of isotypes common to other eutherian mammals. The piglet models offers advantage over rodent models since the fetal repertoire develops without maternal influences and the precocial nature of their multiple offspring allows the experimenter to control the influences of environmental and maternal factors on repertoire development postnatally. B cell lymphogenesis in swine begins in the fetal yolk sac at 20 days of gestation (DG), moves to the fetal liver at 30 DG and eventually to the bone marrow which dominates until birth (114 DG) and to at least 5 weeks postpartum. There is no evidence that the ileal Peyers patches are a site of B cell lymphogenesis or are required for B cell maintenance. Unlike rodents and humans, light chain rearrangement begins first in the lambda locus; kappa rearrangements are not seen until late gestation. Dissimilar to lab rodents and more in the direction of the rabbit, swine utilize a small number of VH genes to form >90% of their pre-immune repertoire. Diversification in response to environmental antigen does not alter this pattern and is achieved by somatic hypermutation (SHM) of the same small number of VH genes. The situation for light chains is less well studied, but certain Vκ and Jκ and Vλ and Jλ are dominant in transcripts and in contrast to rearranged heavy chains, there is little junctional diversity, less SHM, and mutations are not concentrated in CDR regions. The transcribed and secreted pre-immune antibodies of the fetus include mainly IgM, IgA, and IgG3; this last isotype may provide a type of first responder mucosal immunity. Development of functional adaptive immunity is dependent on bacterial MAMPs or MAMPs provided by viral infections, indicating the importance of innate immunity for development of adaptive immunity. The structural analysis of Ig genes of this species indicate that especially the VH and Cγ gene are the result of tandem gene duplication in the context of genomic gene conversion. Since only a few of these duplicated VH genes substantially contribute to the antibody repertoire, polygeny may be a vestige from a time before somatic processes became prominently evolved to generate the antibody repertoire. In swine we believe such duplications within the genome have very limited functional significance and their occurrence is therefore overrated.

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Section: Antibody Repertoire Development and The Origin Of The Genomisupporting

confidence: 69%

The Porcine Antibody Repertoire: Variations on the Textbook Theme

Butler¹,

Wertz²

2012

Front. Immun.

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“…The current characterizations of the porcine immunoglobulin heavy (IGH) locus on chromosome 7 include 15 IGHV genes, four IGHD genes, five IGHJ genes, and the constant genes (Eguchi-Ogawa et al 2012; Eguchi-Ogawa et al 2010). It is likely however, that additional IGHV genes exist upstream from the fifteen that are characterized based on cDNA evidence (Eguchi-Ogawa et al 2010).…”

Section: Brief Communicationmentioning

confidence: 99%

Characterization of a polymorphic IGLV gene in pigs (Sus scrofa)

Schwartz

Murtaugh

2014

Immunogenetics

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Swine, unlike other artiodactyls, but similar to humans, utilize both lambda and kappa light chain isotypes almost equally in the generation of their antibody repertoire. The porcine antibody light chain loci have previously been characterized in a single Duroc sow in which was seen extensive allelic variation between light chain genes on homologous chromosomes. However, the extent of variation between individuals is completely unknown. Using deep sequencing of cDNA-derived amplicons from five pigs, we report the identification and characterization of an IGLV gene that is functional and highly expressed in some animals, yet completely absent in others. Our findings provide a possible rationale for the known individual-to-individual variation in antibody responses to vaccination, infectious challenge and subsequent disease outcome.

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“…Notably, IgG3 has motifs that can interact with complement and Fc␥Rs [116]. It is of some interest that IgG3 in swine, cattle, mice, and humans is the 5=-most C␥ gene and is immediately adjacent to C␦ [117] (Fig. 9).…”

Section: What Is the Real Function Of The Artiodactyl Ipp?mentioning

confidence: 99%

The enigma of the lower gut-associated lymphoid tissue (GALT)

Butler

Šinkora

2013

Journal of Leukocyte Biology

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Artiodactyls possess GALT that appears in fetal life and is located at the extreme end of the ileum. These IPP contain mostly B cells and involute early in postnatal life. Rabbits have a similarly located lymphoid organ, called the sacculus rotundus. Studies in sheep and rabbits have led to the concept that the lower hindgut GALT represents primary lymphoid tissue for B cells and is necessary for normal B cell development, analogous to the bursa of Fabricius. This review traces the history of the observations and theories that have led to the existing concept concerning the role of lower GALT. We then review recent data from piglets with resected IPP that challenges the concept that the IPP is primary B cell lymphoid tissue and that artiodactyls and rabbits are members of the GALT group in the same context as gallinaceous birds. Eliminating the IPP as the primary lymphoid tissue for B cells leads to the hypothesis that the IPP acts as first-responder mucosal lymphoid tissue.

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Structure of the genomic sequence comprising the immunoglobulin heavy constant (IGHC) genes from Sus scrofa

Cited by 26 publications

References 52 publications

The Porcine Antibody Repertoire: Variations on the Textbook Theme

The Porcine Antibody Repertoire: Variations on the Textbook Theme

Characterization of a polymorphic IGLV gene in pigs (Sus scrofa)

The enigma of the lower gut-associated lymphoid tissue (GALT)

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