Rap1 signal controls B cell receptor repertoire and generation of self-reactive B1a cells

Immunity
Daisuke IshidaNagahiro Minato

Abstract

We previously reported that the mice deficient for SPA-1, a Rap1 GTPase-activating protein, developed hematopoietic stem cell disorders. Here, we demonstrate that SPA-1(-/-) mice show an age-dependent increase in B220(high) B1a cells producing anti-dsDNA antibody and lupus-like nephritis. SPA-1(-/-) peritoneal B1 cells revealed the altered Vkappa gene repertoire, including skewed Vkappa4 usage and the significant Igkappa/Iglambda isotype inclusion indicative of extensive receptor editing. Rap1GTP induced OcaB gene activation via p38MAPK-dependent Creb phosphorylation, and consistently, SPA-1(-/-) immature BM B cells showing high Rap1GTP exhibited the augmented expression of OcaB and Vkappa4 genes. SPA-1(-/-) BM cells could transfer the autoimmunity in association with the generation of peritoneal B220(high) B1a cells in Rag-2(-/-) recipients. Finally, a portion of SPA-1(-/-) mice developed B1 cell leukemia with hemolytic autoantibody. Present results suggest that the regulated Rap1 signal in the immature B cells plays a role in modifying the B cell receptor repertoire and in maintaining the self-tolerance.

References

Jan 1, 1988·Annual Review of Immunology·K Hayakawa, R R Hardy
Jan 26, 1995·Nature·M GstaigerC M Hovens
Dec 1, 1996·European Journal of Immunology·P J NielsenW Schaffner
Jan 1, 1997·Immunity·C ChenM Weigert
Oct 9, 1998·The Journal of Experimental Medicine·M W Retter, D Nemazee
Jun 22, 1999·The Journal of Biological Chemistry·N TsukamotoN Minato
Feb 7, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J J KennyD L Longo
Jun 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S StevensR G Roeder
Feb 27, 2001·Science·R CasellasM C Nussenzweig
Jan 5, 2002·Immunity·H LiM Weigert
Jan 24, 2002·The Journal of Experimental Medicine·Yijin LiMartin Weigert
May 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·Roberta BichiCarlo M Croce
Aug 31, 2002·Hematological Oncology·Gerassimos A PangalisMaria K Angelopoulou
Feb 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jian SunPatrick Matthias
Mar 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karl BalabanianDominique Emilie
Mar 12, 2003·Cell·Vijay YajnikDaniel A Haber
Aug 15, 2003·International Immunology·Mila Jankovic, Michel C Nussenzweig
Aug 16, 2003·Science·Hedda WardemannMichel C Nussenzweig
Sep 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Daisuke IshidaNagahiro Minato
Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhiyan LiangChandra Mohan
Sep 25, 2003·Nature Reviews. Molecular Cell Biology·Johannes L Bos
Nov 11, 2003·Journal of Biochemistry·Masakazu Hattori, Nagahiro Minato
Mar 23, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephanie AtencioBrian L Kotzin
Aug 3, 2004·Nature Neuroscience·Jens C Schwamborn, Andreas W Püschel
Aug 18, 2004·Trends in Molecular Medicine·Kohei KometaniNagahiro Minato
Aug 31, 2004·Nature Medicine·Jill R CrittendenAnn M Graybiel
Oct 19, 2004·Cancer Cell·Lourdes PlanellesMichael Hahne
Jan 22, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey S RiceBetty Diamond

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Citations

Apr 23, 2013·Experimental Cell Research·Nagahiro Minato
Apr 5, 2012·The Journal of Experimental Medicine·Bojan VilagosMeinrad Busslinger
Oct 24, 2012·The Journal of Experimental Medicine·Marc SeifertRalf Küppers
Nov 14, 2007·PLoS Pathogens·Kathy H Y ShairNancy Raab-Traub
Jul 14, 2010·Future Oncology·Makoto NodaHitoshi Kitayama
Apr 4, 2007·Proceedings of the National Academy of Sciences of the United States of America·Lynda MazariMoncef Zouali
Feb 9, 2008·Trends in Immunology·Moncef Zouali
Nov 29, 2008·Cancer Science·Nagahiro Minato, Masakazu Hattori
Aug 2, 2006·Current Opinion in Immunology·Richard R Hardy
Jun 25, 2015·Journal of Autoimmunity·Kirsten A FairfaxFabienne Mackay
Jun 12, 2013·Journal of Immunotoxicology·Jean C PfauRyan Marcum
Jan 9, 2007·Molecular Immunology·Cristina M ContrerasAnne B Satterthwaite
Feb 23, 2012·Hypertension·Federico JensenAna Claudia Zenclussen
Jun 28, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Derek S PyeKathleen J Till
Mar 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yougui XiangWilliam T Garrard
Apr 21, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·María C Amezcua VeselyAdriana Gruppi
Oct 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Caylib A DurandMichael R Gold
Aug 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Haiyan ChuSubramaniam Malarkannan
Jan 9, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yougui XiangWilliam T Garrard
Sep 5, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yougui XiangWilliam T Garrard
Feb 13, 2015·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Ai-Ping FengLi Su
Jun 19, 2021·Frontiers in Immunology·Sayaka IshiharaKoko Katagiri

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