The little brown bat, M. lucifugus, displays a highly diverse VH, DH and JH repertoire but little evidence of somatic hypermutation

Bratsch, Sara; Wertz, Nancy; Chaloner, Kathryn; Kunz, Thomas; Butler, John E.

doi:10.1016/j.dci.2010.06.004

Cited by 54 publications

(53 citation statements)

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“…In fact there is evidence that the genes segments encoding these duplicated VH genes and several others were duplicated as a block (Eguchi-Ogawa et al, 2010) similar to the duplicons in the human heavy chain constant region and the JλCλ loci of all studied mammals (Figure 1B). These features of duplicated genes are also seen among the VH genes of bats (Bratsch et al, 2011; Butler et al, 2011d). These comparisons support the hypothesis that the germline VH repertoire in swine results from gene duplication that occurred simultaneously with genomic gene conversion.…”

Section: Antibody Repertoire Development and The Origin Of The Genomimentioning

confidence: 83%

“…The genome of Xenopus tropicalis contains 11 VH gene families and 37 Vλ genes encoded at three loci (Qin et al, 2008). Among eutherian mammals, some bats have >250 VH genes, lab rodents and human ∼100, and rabbits ∼200 (Bratsch et al, 2011; Table 1). Many of these VH genes are known to be pseudogenes, consistent with data on tandem gene duplication (Wolfe and Shields, 1997).…”

Section: Antibody Repertoire Development and The Origin Of The Genomimentioning

confidence: 99%

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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 Genomimentioning

confidence: 83%

Section: Antibody Repertoire Development and The Origin Of The Genomimentioning

confidence: 99%

The Porcine Antibody Repertoire: Variations on the Textbook Theme

Butler¹,

Wertz²

2012

Front. Immun.

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“…The program is therefore applicable to the construction of VH databases for species where little genomic sequence is currently available. Studies of B cell biology in non-human or mouse contexts are, to date, less common, in part owing to a lack of familiarity with the genetics of other model organisms101920. Extending antibody repertoire analysis to multiple new species, however, will expand the possibilities for immunological research of relevance for studies of human pathogens, such as those currently performed in voles (hantavirus)21, ferrets (influenza virus)22 or different non-human primate species (Ebolavirus and many other infections)23.…”

Section: Discussionmentioning

confidence: 99%

Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity

et al. 2016

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Comprehensive knowledge of immunoglobulin genetics is required to advance our understanding of B cell biology. Validated immunoglobulin variable (V) gene databases are close to completion only for human and mouse. We present a novel computational approach, IgDiscover, that identifies germline V genes from expressed repertoires to a specificity of 100%. IgDiscover uses a cluster identification process to produce candidate sequences that, once filtered, results in individualized germline V gene databases. IgDiscover was tested in multiple species, validated by genomic cloning and cross library comparisons and produces comprehensive gene databases even where limited genomic sequence is available. IgDiscover analysis of the allelic content of the Indian and Chinese-origin rhesus macaques reveals high levels of immunoglobulin gene diversity in this species. Further, we describe a novel human IGHV3-21 allele and confirm significant gene differences between Balb/c and C57BL6 mouse strains, demonstrating the power of IgDiscover as a germline V gene discovery tool.

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“…5). As shown, many of these share common FR1 sequences, a smaller number share CDR1, FR2 and CDR2 while the greatest diversity is seen in FR3 (Bratsch et al, 2011). This pattern of similarity among duplicated Ig genes is also seen in human and mouse, suggesting that after duplication and genomic gene conversion, the 3' segment was subjected to a higher rate of germline mutation and selection.…”

Section: Duplication and Diversification Of Ig Genesmentioning

confidence: 75%

“…Myotis lucifugus has >250 VH3 family genes (Fig. 5) and probably 350 total VH genes, including all families (Bratsch et al, 2011). However, SHM occurs at the frequency seen in fetal piglets (Fig.…”

Section: Are Multiple V H Genes Required For Host Immune Protection?mentioning

confidence: 99%