Constitutive activation of Bruton's tyrosine kinase induces the formation of autoreactive IgM plasma cells

European Journal of Immunology
Rogier KersseboomR W Hendriks

Abstract

B-cell receptor (BCR)-mediated signals provide the basis for B-cell differentiation in the BM and subsequently into follicular, marginal zone, or B-1 B-cell subsets. We have previously shown that B-cell-specific expression of the constitutive active E41K mutant of the BCR-associated molecule Bruton's tyrosine kinase (Btk) leads to an almost complete deletion of immature B cells in the BM. Here, we report that low-level expression of the E41K or E41K-Y223F Btk mutants was associated with reduced follicular B-cell numbers and significantly increased proportions of B-1 cells in the spleen. Crosses with 3-83 mu delta and VH81X BCR Tg mice showed that constitutive active Btk expression did not change follicular, marginal zone, or B-1 B-cell fate choice, but resulted in selective expansion or survival of B-1 cells. Residual B cells were hyperresponsive and manifested sustained Ca(2+) mobilization. They were spontaneously driven into germinal center-independent plasma cell differentiation, as evidenced by increased numbers of IgM(+) plasma cells in spleen and BM and significantly elevated serum IgM. Because anti-nucleosome autoantibodies and glomerular IgM deposition were present, we conclude that constitutive Btk activation causes de...Continue Reading

References

Nov 28, 1991·Nature·D M RussellD Nemazee
Sep 1, 1995·Immunity·W N KhanL A Herzenberg
Jul 3, 1999·Science·K HayakawaR R Hardy
Aug 10, 2000·Immunity·D A FrumanO N Witte
Feb 13, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·Y QianS H Clarke
Mar 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sabine MiddendorpRudolf W Hendriks
Dec 18, 2002·The Journal of Experimental Medicine·Margaret L HibbsDavid M Tarlinton
Feb 4, 2003·Nature Immunology·Amy N AnzelonRobert C Rickert
Mar 5, 2003·The Journal of Experimental Medicine·Akira SuzukiToru Nakano
Jul 2, 2003·The Journal of Experimental Medicine·Rogier KersseboomRudolf W Hendriks
Aug 16, 2003·Science·Hedda WardemannMichel C Nussenzweig
Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sabine MiddendorpRudolf W Hendriks
Feb 6, 2004·Nature Immunology·Stefano CasolaKlaus Rajewsky
Dec 22, 2004·Springer Seminars in Immunopathology·Jessica J MansonMichael R Ehrenstein
Mar 18, 2005·Annual Review of Immunology·Hassan JumaaMichael Reth
May 12, 2005·Current Opinion in Immunology·Lars Nitschke
Sep 20, 2005·Immunity·Lijun WenKyoko Hayakawa
Feb 27, 2007·Nature Immunology·Zou XiangKenneth G C Smith
Apr 25, 2008·Current Opinion in Immunology·David Allman, Shiv Pillai
Mar 18, 2009·Immunological Reviews·Tomohiro Kurosaki, Masaki Hikida
Jul 8, 2009·Nature Reviews. Rheumatology·Thomas DörnerGerd R Burmester
Jul 15, 2009·Immunological Reviews·Lars Nitschke
Nov 3, 2009·Cell·Lakshmi SrinivasanKlaus Rajewsky
Dec 18, 2009·Nature Immunology·Harald von Boehmer, Fritz Melchers

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Citations

Feb 13, 2016·Expert Review of Clinical Immunology·Leslie J CroffordPeggy L Kendall
Jun 19, 2013·International Reviews of Immunology·Laurens P Kil, Rudi W Hendriks
Jun 4, 2011·Expert Opinion on Therapeutic Targets·Rudi W HendriksFrank Jt Staal
Dec 1, 2014·Virchows Archiv : an International Journal of Pathology·Iván Fernández-VegaTeresa Marafioti
Aug 5, 2006·Experimental Cell Research·Kristen FrenzelPeter P Sayeski
Feb 20, 2018·Molecular Cancer·Simar Pal SinghRudi W Hendriks
Jan 6, 2018·Nature Reviews. Cancer·Markus Müschen
Jun 15, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wei LuoLee Ann Garrett-Sinha
Aug 30, 2020·American Journal of Clinical Dermatology·Emily M Altman
Jul 26, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica MayeuxAnne B Satterthwaite
Aug 12, 2017·Expert Review of Clinical Immunology·Matthias CassiaDavid Jayne
Jul 13, 2021·Frontiers in Cell and Developmental Biology·Lauren E KuefferAmy H Andreotti
Jun 20, 2021·Brain : a Journal of Neurology·Kathryn PellerinMichael Mingueneau
Jul 6, 2021·Current Pharmaceutical Design·Anja SteinmaurerJohann Sellner

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