Effect of cell:cell competition and BAFF expression on peripheral B cell tolerance and B-1 cell survival in transgenic mice expressing a low level of Igkappa-reactive macroself antigen

European Journal of Immunology
Djemel Aït-AzzouzeneDavid Nemazee

Abstract

In mice carrying a synthetic Igkappa-reactive superantigen ("kappa macroself antigen"), low level expression induced split peripheral B cell tolerance in the sIgkappa+ compartment, with striking reductions in follicular and marginal zone (MZ) B cells and the retention of significant numbers of sIgkappa+ B-1a but not B-1b cells in the peritoneum. Here, we characterize the transgenic line pKkappa with this split tolerance phenotype and assess the effects of B cell competition and the survival cytokine BAFF (B cell activating factor belonging to the TNF family) on peripheral tolerance. In pKkappa mice the surviving peritoneal and splenic kappa+ B cells were largely lost in mice carrying one copy of the human Ckappa exon in place of the mouse version, a maneuver that generates additional antigen non-reactive competitor B cells in this model. Furthermore, overexpression of BAFF suppressed kappa-macroself antigen-induced deletion and promoted production of both IgM,kappa and IgA,kappa antibodies in mice with normal Igkappa alleles but not in mice carrying one copy of the human Ckappa allele. These findings suggest that BAFF overexpression has minimal effects on the survival of autoreactive B cells in a polyclonal immune system and th...Continue Reading

References

Jan 1, 1992·Annual Review of Immunology·C C Goodnow
Aug 8, 1991·Nature·C C GoodnowE Adams
Nov 28, 1991·Nature·D M RussellD Nemazee
Aug 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·E AdamsC C Goodnow
Jan 1, 1983·Annual Review of Immunology·G J Nossal
Jan 1, 1994·Annual Review of Immunology·M Z Radic, M Weigert
Jan 1, 1994·The Journal of Experimental Medicine·D A Fulcher, A Basten
Dec 10, 1999·The Journal of Experimental Medicine·F MackayJ L Browning
Jun 3, 2000·Annual Review of Immunology·D Nemazee
Oct 4, 2000·The Journal of Experimental Medicine·R K DoS Chen-Kiang
Nov 21, 2000·The Journal of Experimental Medicine·M BattenF Mackay
Dec 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·J ZhangT Zhou
Feb 27, 2001·Science·R CasellasM C Nussenzweig
Apr 12, 2002·Nature·Elizabeth A LeadbetterAnn Marshak-Rothstein
Jul 13, 2002·European Journal of Immunology·Antonius G RolinkFritz Melchers
Aug 3, 2002·Nature Immunology·Mikhail B LitinskiyAndrea Cerutti
Jan 15, 2003·Annals of the Rheumatic Diseases·X MarietteR Kimberly
Jun 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Susan Harless Smith, Michael P Cancro
Aug 16, 2003·Science·Hedda WardemannMichel C Nussenzweig
Sep 17, 2003·The Journal of Experimental Medicine·Leonid GorelikMartin L Scott
Jul 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lai Guan NgCharles R Mackay
Sep 16, 2004·European Journal of Immunology·Qunrui YeWayne W Hancock
Jun 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amanda L GavinDavid Nemazee

❮ Previous
Next ❯

Citations

May 31, 2008·Archivum Immunologiae Et Therapiae Experimentalis·Laura S TremlMichael P Cancro
Apr 27, 2012·Current Rheumatology Reports·Anne Davidson
Nov 27, 2008·Cell Biochemistry and Biophysics·John F TremlMichael P Cancro
Jun 13, 2009·Nature Reviews. Immunology·Fabienne Mackay, Pascal Schneider
Jul 5, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yijin LiAnita S Chong
Aug 2, 2006·The Journal of Experimental Medicine·Laura Mandik-NayakPaul M Allen
Aug 20, 2008·The Journal of Experimental Medicine·John B CareyAnn J Feeney
Nov 18, 2009·The Journal of Experimental Medicine·Michael W TuscheTak W Mak
Dec 26, 2012·The Journal of Experimental Medicine·Sarah F AndrewsPatrick C Wilson
Feb 18, 2006·The Journal of Clinical Investigation·Meera RamanujamAnne Davidson
May 5, 2009·The Journal of Clinical Investigation·Michael P CancroMunther A Khamashta
Nov 26, 2013·The Journal of Clinical Investigation·Stefanie Sarantopoulos, Maureen A Su
Feb 14, 2014·Expert Opinion on Therapeutic Targets·William Stohl
Jul 26, 2006·Pharmacology & Therapeutics·Andrew P R SutherlandCharles R Mackay
Oct 28, 2006·Experimental Gerontology·Daniela FrascaBonnie B Blomberg
Mar 9, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Clare A NotleyMichael R Ehrenstein
Sep 8, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Miyo OtaDavid Nemazee
May 4, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chao JiangLoren D Erickson
Mar 17, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bao Hoa DuongDavid Nemazee
Jun 15, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Caroline GrönwallGregg J Silverman

❮ Previous
Next ❯

Related Concepts

Related Feeds

B cell Tolerance

B cell tolerance is maintained through mechanisms that can reversibly or irreversibly silence autoreactive B lymphocytes. Here is the latest research.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.