Ku80 is required for immunoglobulin isotype switching

The EMBO Journal
R CasellasMichel C Nussenzweig

Abstract

Isotype switching is the DNA recombination mechanism by which antibody genes diversify immunoglobulin effector functions. In contrast to V(D)J recombination, which is mediated by RAG1, RAG2 and DNA double-stranded break (DSB) repair proteins, little is known about the mechanism of switching. We have investigated the role of DNA DSB repair in switch recombination in mice that are unable to repair DSBs due to a deficiency in Ku80 (Ku80(-/-)). B-cell development is arrested at the pro-B cell stage in Ku80(-/-) mice because of abnormalities in V(D)J recombination, and there are no mature B cells. To reconstitute the B-cell compartment in Ku80(-/-) mice, pre-rearranged VB1-8 DJH2 (mu i) and V3-83JK2 (kappa i) genes were introduced into the Ku80(-/-) background (Ku80(-/-)mu i/+kappa i/+). Ku80(-/-)mu i/+ kappai/+ mice develop mature mIgM+ B cells that respond normally to lipopolysaccharide (LPS) or LPS plus interleukin-4 (IL-4) by producing specific germline Ig constant region transcripts and by forming switch region-specific DSBs. However, Ku80(-/-)mu i/+kappa i/+ B cells are unable to produce immunoglobulins of secondary isotypes, and fail to complete switch recombination. Thus, Ku80 is essential for switch recombination in vivo, s...Continue Reading

References

May 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·T Honjo, T Kataoka
Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·C C ChuE E Max
May 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·E A HendricksonD T Weaver
Apr 14, 1983·Nature·S Tonegawa
Jan 24, 1980·Nature·T H RabbittsD L Bentley
Mar 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·C ColecloughR P Perry
Apr 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·M ObataT Honjo
Feb 10, 1983·Nature·G C BosmaM J Bosma
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·D B RothM Gellert
Nov 1, 1995·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·P A JeggoS P Jackson
Jun 14, 1996·The Journal of Biological Chemistry·F Liang, M Jasin
Apr 1, 1996·Current Opinion in Immunology·J Stavnezer
Aug 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·F LiangM Jasin
Mar 1, 1997·Immunity·E SonodaK Rajewsky
Sep 18, 1997·The Journal of Experimental Medicine·H OuyangG C Li

❮ Previous
Next ❯

Citations

Jun 26, 1999·European Journal of Immunology·T BorggrefeR Jessberger
Feb 6, 2002·Springer Seminars in Immunopathology·N S Longo, P E Lipsky
Dec 4, 2003·Molecular Immunology·Stephen J ZoogMarilyn R Kehry
Nov 13, 2002·Mutation Research·Mark O'Driscoll, Penny Jeggo
Apr 2, 2003·Journal of Neuroimmunology·Foroozan MokhtarianCedric S Raine
Mar 19, 1999·Immunology Today·B G MagorG W Warr
Mar 8, 2002·Experimental Hematology·Yu-Tzu TaiKenneth C Anderson
Sep 7, 2001·Current Opinion in Immunology·A Durandy, T Honjo
Mar 14, 2003·Current Opinion in Immunology·Amy L Kenter
Mar 14, 2000·Current Opinion in Immunology·K Kinoshita, T Honjo
May 14, 1999·Current Opinion in Immunology·M WablC Steinberg
Jun 27, 2003·Trends in Biochemical Sciences·Michael S NeubergerSvend K Petersen-Mahrt
Jan 26, 2002·Journal of Photochemistry and Photobiology. B, Biology·P A Jeggo, P Concannon
Jan 22, 2002·Trends in Immunology·John P ManisFrederick W Alt
Jul 4, 2001·Nature Reviews. Molecular Cell Biology·K Kinoshita, T Honjo
Jul 21, 2007·Nature Immunology·Mila JankovicMichel C Nussenzweig
Jan 30, 2008·Nature Reviews. Genetics·Andrés Aguilera, Belén Gómez-González
Jul 2, 2004·Nature Reviews. Immunology·Jayanta Chaudhuri, Frederick W Alt
Jun 26, 2012·Nature Reviews. Immunology·Zhenming XuPaolo Casali
Nov 20, 2002·British Journal of Haematology·Uwe M MartensWinand Lange
Mar 6, 2003·Reviews in Clinical and Experimental Hematology·Deepak GuptaKenneth C Anderson
Jul 7, 2000·The New England Journal of Medicine·P J Delves, I M Roitt
Aug 20, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nasim A BegumTasuku Honjo
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Cristian BoboilaFrederick W Alt
Jun 24, 1998·The Journal of Experimental Medicine·J P ManisF W Alt
Aug 3, 1999·The Journal of Experimental Medicine·A L Kenter
Aug 3, 1999·The Journal of Experimental Medicine·C E SchraderJ Stavnezer
Apr 19, 2000·The Journal of Experimental Medicine·A ShanmugamA L Kenter
Aug 8, 2001·The Journal of Experimental Medicine·C G LeeT Honjo
Dec 4, 2002·The Journal of Experimental Medicine·Gayle C BosmaMelvin J Bosma
May 8, 2002·The Journal of Experimental Medicine·Katrin F ChuaJohn P Manis
May 14, 2003·The Journal of Experimental Medicine·Carol E SchraderJanet Stavnezer
Jun 18, 2003·The Journal of Experimental Medicine·Bernardo Reina-San-MartinMichel C Nussenzweig
Oct 22, 2003·The Journal of Experimental Medicine·Alberto MartinMatthew D Scharff
Oct 27, 2004·The Journal of Experimental Medicine·Joanne M LumsdenRichard J Hodes

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.