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Non-coding Class Switch Recombination-related transcription in human normal and pathological immune responses | L. Collado-Torres

lcolladotor.github.io
Background: Antibody class switch recombination (CSR) to IgG, IgA or IgE is a hallmark of adaptive immunity, allowing antibody function diversification beyond IgM. CSR involves a deletion of the IgM/IgD constant region genes placing a new acceptor Constant (CH) gene, downstream of the VDJH exon. CSR depends on non-coding (CSRnc) transcription of donor Iμ and acceptor IH exons, located 5′ upstream of each CH coding gene. Although our knowledge of the role of CSRnc transcription has advanced greatly, its extension and importance in healthy and diseased humans is scarce. Methods: We analyzed CSRnc transcription in 70,603 publicly available RNA-seq samples, including GTEx, TCGA and the Sequence Read Archive (SRA) using recount2, an online resource consisting of normalized RNA-seq gene and exon counts, as well as coverage BigWig files that can be programmatically accessed through R. CSRnc transcription was validated with a qRT-PCR assay for Iμ, Iγ1 and Iγ3 in humans in response to vaccination. Results: We mapped IH transcription for the human IgH locus, including the less understood IGHD gene. CSRnc transcription was restricted to B cells and is widely distributed in normal adult tissues, but predominant in blood, spleen, MALT-containing tissues, visceral adipose tissue and some so-called 'immune privileged' tissues. However, significant Iγ4 expression was found even in non-lymphoid fetal tissues. CSRnc expression in cancer tissues mimicked the expression of their normal counterparts, with notable pattern changes in some common cancer subsets. CSRnc transcription in tumors appears to result from tumor infiltration by B cells, since CSRnc transcription was not detected in corresponding tumor-derived immortal cell lines. Additionally, significantly increased Iδ transcription in ileal mucosa in Crohn's disease with ulceration was found. Conclusions: CSRnc transcription occurs in multiple anatomical locations beyond classical secondary lymphoid organs, representing a potentially useful marker of effector B cell responses in normal and pathological immune responses. The pattern of IH exon expression may reveal clues of the local immune response (i.e. cytokine milieu) in health and disease. This is a great example of how the public recount2 data can be used to further our understanding of transcription, including regions outside the known transcriptome.
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Title Non-coding Class Switch Recombination-related transcription in human normal and pathological immune responses | L. Collado-Torres
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Keywords cloud transcription CSRnc tissues gene normal expression including responses immune IH CSR exon Preprint pattern cancer RNAseq Leonardo humans cell
Keywords consistency
Keyword Content Title Description Headings
transcription 12
CSRnc 9
tissues 5
gene 4
normal 4
expression 4
Headings
H1 H2 H3 H4 H5 H6
1 0 1 1 0 0
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Keyword Occurrence Density
transcription 12 0.60 %
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tissues 5 0.25 %
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Keyword Occurrence Density Possible Spam
CSRnc transcription was 3 0.15 % No
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and pathological immune responses 2 0.10 % No
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transcription in tumors appears 1 0.05 % No
CSRnc transcription in tumors 1 0.05 % No

Internal links in - lcolladotor.github.io

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Non-codingMatriculationSwitch Recombination-related transcription in human normal and pathological immune responses | L. Collado-Torres Toggle navigation L. Collado-Torres Home Publications Talks Blog CV Students Teaching Contact Search Non-codingMatriculationSwitch Recombination-related transcription in human normal and pathological immune responses Helena Kuri-Magaña, Leonardo Collado-Torres, Andrew E Jaffe, Humberto Valdovinos-Torres, Marbella Ovilla-Muñoz, Juan M Téllez-Sosa, Laura C Bonifaz-Alfonzo, Jesús Martínez-Barnetche Abstract Background:Pathogenmatriculation switch recombination (CSR) to IgG, IgA or IgE is a hallmark of adaptive immunity, permitting pathogen function diversification vastitude IgM. CSR involves a deletion of the IgM/IgD unvarying region genes placing a new acceptorUnvarying(CH) gene, downstream of the VDJH exon. CSR depends on non-coding (CSRnc) transcription of donor Iμ and acceptor IH exons, located 5′ upstream of each CH coding gene. Although our knowledge of the role of CSRnc transcription has wide greatly, its extension and importance in healthy and diseased humans is scarce. Methods: We analyzed CSRnc transcription in 70,603 publicly misogynist RNA-seq samples, including GTEx, TCGA and the Sequence Read Archive (SRA) using recount2, an online resource consisting of normalized RNA-seq gene and exon counts, as well as coverage BigWig files that can be programmatically accessed through R. CSRnc transcription was validated with a qRT-PCR reconnaissance for Iμ, Iγ1 and Iγ3 in humans in response to vaccination. Results: We mapped IH transcription for the human IgH locus, including the less understood IGHD gene. CSRnc transcription was restricted to B cells and is widely distributed in normal sultana tissues, but predominant in blood, spleen, MALT-containing tissues, visceral upholstered tissue and some so-called 'immune privileged' tissues. However, significant Iγ4 expression was found plane in non-lymphoid fetal tissues. CSRnc expression in cancer tissues mimicked the expression of their normal counterparts, with notable pattern changes in some worldwide cancer subsets. CSRnc transcription in tumors appears to result from tumor infiltration by B cells, since CSRnc transcription was not detected in respective tumor-derived immortal lamina lines. Additionally, significantly increased Iδ transcription in ileal mucosa in Crohn's disease with ulceration was found. Conclusions: CSRnc transcription occurs in multiple corporeal locations vastitude classical secondary lymphoid organs, representing a potentially useful marker of effector B lamina responses in normal and pathological immune responses. The pattern of IH exon expression may reveal clues of the local immune response (i.e. cytokine milieu) in health and disease. This is a unconfined example of how the public recount2 data can be used to remoter our understanding of transcription, including regions outside the known transcriptome. Type Pre-print Publication bioRxiv 384172 Date August, 2018 Links PDF Pre-print © 2011-2018 Leonardo Collado Torres under (CC) BY-NC-SA 4.0. All thoughts and opinions here are my own. · Powered by the Academic theme for Hugo. × Cite Copy Download