Evidence map›Paper›PMID 9625768›Full record

ArticleThe Journal of experimental medicine1998

Ku70 is required for late B cell development and immunoglobulin heavy chain class switching.

J P Manis, Y Gu, R Lansford, E Sonoda, R Ferrini, L Davidson, K Rajewsky, F W Alt

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed
7.1field-weighted citation impact, top 2% 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

109 citing papers in PubMed, 290 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. DNA Damage Response and Repair in Adaptive Immunity.Frontiers in cell and developmental biology · 2022
    Review
  7. Article
  8. Deficiency of Ku Induces Host Cell Exploitation in Human Cancer Cells.Frontiers in cell and developmental biology · 2021
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Immunodeficiency in Bloom's Syndrome.Journal of clinical immunology · 2018
    Article
  14. Article
  15. Physiological Roles of DNA Double-Strand Breaks.Journal of nucleic acids · 2017
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. IgH chain class switch recombination: mechanism and regulation.Journal of immunology (Baltimore, Md. : 1950) · 2014
    Review

49 more citing papers are in PubMed but not listed here.

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

8 authors at 3 institutions in 3 countries.

J P ManisHoward Hughes Medical Institute, Boston, Massachusetts 02115, USA.
Y Gu
R Lansford
E Sonoda
R Ferrini
L Davidson
K Rajewsky
F W Alt
Boston Children's Hospital · USHoward Hughes Medical Institute · USUniversity of Cologne · DE

Funding

Transcriptional Regulation of the Allergic ResponseP01AI031541 · NIAID · CHILDREN'S HOSPITAL BOSTON · PI GEHA, RAIF SALIM · 1999 to 2007
$8.0M
CONTROL IG HEAVY CHAIN CLASS SWITCHINGK11AI001285 · NIAID · CHILDREN'S HOSPITAL BOSTON · PI MANIS, JOHN P · 1994 to 1999
–
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-01285NIAID NIH HHS AI-240047NIAID NIH HHS AI-31541NIAID NIH HHS P01 AI031541NIAID NIH HHS U19 AI031541
6 · The paper itself

Abstract

Immunoglobulin (Ig) heavy chain (HC) class switch recombination (CSR) is a late B cell process that involves intrachromosomal DNA rearrangement. Ku70 and Ku80 form a DNA end-binding complex required for DNA double strand break repair and V(D)J recombination. Ku70(-/-) (K70T) mice, like recombination activating gene (RAG)-1- or RAG-2-deficient (R1T or R2T) mice, have impaired B and T cell development at an early progenitor stage, which is thought to result at least in part from defective V(D)J recombination (Gu, Y., K.J. Seidl, G.A. Rathbun, C. Zhu, J.P. Manis, N. van der Stoep, L. Davidson, H.L. Cheng, J.M. Sekiguchi, K. Frank, et al. 1997. Immunity. 7:653-665; Ouyang, H., A. Nussenzweig, A. Kurimasa, V.C. Soares, X. Li, C. Cordon-Cardo, W. Li, N. Cheong, M. Nussenzweig, G. Iliakis, et al. 1997. J. Exp. Med. 186:921-929). Therefore, to examine the potential role of Ku70 in CSR, we generated K70T mice that carry a germline Ig HC locus in which the JH region was replaced with a functionally rearranged VH(D)JH and Ig lambda light chain transgene (referred to as K70T/HL mice). Previously, we have shown that B cells from R1T or R2T mice carrying these rearranged Ig genes (R1T/HL or R2T/HL mice) can undergo CSR to IgG isotypes (Lansford, R., J. Manis, E. Sonoda, K. Rajewsky, and F. Alt. 1998. Int. Immunol. 10:325-332). K70T/HL mice had significant numbers of peripheral surface IgM+ B cells, which generated serum IgM levels similar to those of R2T/HL mice. However, in contrast to R2T/HL mice, K70T/HL mice had no detectable serum IgG isotypes. In vitro culture of K70T/HL B cells with agents that induce CSR in normal or R2T/HL B cells did lead to the induction of germline CH transcripts, indicating that initial signaling pathways for CSR were intact in K70T/HL cells. However, treatment with such agents did not lead to detectable CSR by K70T/HL B cells, and instead, led to cell death within 72 h. We conclude that Ku70 is required for the generation of B cells that have undergone Ig HC class switching. Potential roles for Ku70 in the CSR process are discussed.

Indexed as

Antigens, NuclearDNA HelicasesImmunoglobulin Class SwitchingAnimalsB-LymphocytesDNA-Binding ProteinsHematopoietic Stem CellsImmunoglobulin GImmunoglobulin Heavy ChainsImmunoglobulin IsotypesImmunoglobulin Light ChainsKu AutoantigenMiceMice, Mutant StrainsMice, TransgenicNuclear ProteinsAntigens, NuclearDNA-Binding ProteinsDNA HelicasesImmunoglobulin GImmunoglobulin Heavy ChainsImmunoglobulin IsotypesImmunoglobulin Light ChainsKu AutoantigenNuclear ProteinsXRCC5 protein, humanXrcc6 protein, humanXrcc6 protein, mouse

Identifiers

PMID9625768
PMCPMC2212369
OpenAlexW2097736672

What OpenQuestion holds

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Registered trials

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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.