Evidence map›Paper›PMID 8313911›Full record

ArticleThe EMBO journal1994

S region transcription per se promotes basal IgE class switch recombination but additional factors regulate the efficiency of the process.

A Bottaro, R Lansford, L Xu, J Zhang, P Rothman, F W Alt

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 211 citations in OpenAlex.

  1. Article
  2. Review
  3. Analysis of Chromatin Openness in Testicle Tissue of Yak and Cattle-Yak.International journal of molecular sciences · 2022
    Article
  4. Article
  5. Current insights into the mechanism of mammalian immunoglobulin class switch recombination.Critical reviews in biochemistry and molecular biology · 2019
    Review
  6. Review
  7. Review
  8. Physiological Roles of DNA Double-Strand Breaks.Journal of nucleic acids · 2017
    Review
  9. Class-Switch Recombination in the Absence of the IgH 3' Regulatory Region.Journal of immunology (Baltimore, Md. : 1950) · 2016
    Article
  10. Review
  11. IgH chain class switch recombination: mechanism and regulation.Journal of immunology (Baltimore, Md. : 1950) · 2014
    Review
  12. Review
  13. Review
  14. Reprogramming IgH isotype-switched B cells to functional-grade induced pluripotent stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2012
    Article
  15. Article
  16. Article
  17. Mismatch-mediated error prone repair at the immunoglobulin genes.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2011
    Review
  18. Article
  19. Article
  20. Expression of IgA class switching gene in tonsillar mononuclear cells in patients with IgA nephropathy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2011
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

A BottaroHoward Hughes Medical Institute, Children's Hospital, Boston, MA.
R Lansford
L Xu
J Zhang
P Rothman
F W Alt
Howard Hughes Medical Institute · US

Funding

Mechanisms that Control IgH Variable Region Exon AssemblyR01AI020047 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI ALT, FREDERICK W. · 1985 to 2025
$14.1M
ASSEMBLY AND EXPRESSION OF IG VARIBLE REGION GENESR37AI020047 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI ALT, FREDERICK W · 1991 to 2000
$323k
MOLECULAR MECHANISMS THAT CONTROL IGE-SPECIFIC ANTIBODYR01AI033450 · NIAID · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI ROTHMAN, PAUL B · 1993 to 1996
–
MOLECULAR MECHANISMS THAT CONTROL IGE ANTIBODY RESPONSESR21AI033450 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ROTHMAN, PAUL B · 1997 to 1997
–
MOLECULAR BASIS OF IMMUNE FUNCTION IN HEALTH AND DISEASEU01AI031541 · NIAID · CHILDREN'S HOSPITAL BOSTON · PI GEHA, RAIF SALIM · 1991 to 1994
–
MOLECULAR BASIS OF IMMUNE FUNCTION IN HEALTH AND DISEASEU19AI031541 · NIAID · CHILDREN'S HOSPITAL BOSTON · PI GEHA, RAIF SALIM · 1995 to 1998
–
NIAID NIH HHS AI-20047NIAID NIH HHS AI-31541NIAID NIH HHS AI-33450
6 · The paper itself

Abstract

Stimulation of B lymphocytes with a combination of lipopolysaccharide (LPS) and interleukin-4 (IL-4) induces germline transcription of and subsequent switching to the epsilon heavy chain constant region (C epsilon) gene. Mature germline C epsilon transcripts contain a non-coding exon (I epsilon exon) spliced to the C epsilon exons. To distinguish between the potential roles of germline transcription and those of germline transcripts in regulating the class switch process, we replaced the LPS- and IL-4-inducible I epsilon promoter and exon in ES cells with an LPS-inducible E mu enhancer/VH promoter expression cassette. Wildtype, heterozygous or homozygous mutant ES cells were injected into RAG-2 deficient blastocysts to generate somatic chimeras in which all B cells derived from ES cells. In contrast to normal B cells, heterozygous and homozygous mutant B cells had substantial transcription through the epsilon switch recombination region (S epsilon) following treatment with LPS alone and, under these conditions, both underwent low level switching (10- to 100-fold less than wildtype cells stimulated with LPS + IL-4) to IgE production. Heterozygous mutant cells underwent switching to IgE at essentially wildtype levels when stimulated with LPS and IL-4. However, homozygous mutant cells still showed extremely low levels of switching to IgE upon LPS and IL-4 stimulation. Analyses of hybridomas from heterozygous mutants indicated that the mutation is cis-acting and normal switching to other isotypes indicated that it is specific for IgE. Thus transcription per se generates low levels of class switch recombination in the absence of I region sequences. However, we demonstrate for the first time that, for optimal efficiency, the process requires the presence of the intact I region and/or I region promoter in cis, implicating factors beyond transcription through the S region in the regulation of class switching.

Indexed as

Gene Rearrangement, B-Lymphocyte, Heavy ChainGenes, SwitchTranscription, GeneticAnimalsBase SequenceB-LymphocytesCell LineCloning, MolecularDNAExonsGene Expression RegulationHeterozygoteHomozygoteImmunoglobulin EInterleukin-4LipopolysaccharidesDNAImmunoglobulin EInterleukin-4Lipopolysaccharides

Identifiers

PMID8313911
PMCPMC394857
OpenAlexW107818682

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.