Silencing of autoreactive B cells by anergy: a fresh perspective

Current Opinion in Immunology
Stephen B GauldJohn C Cambier

Abstract

B-cell antigen receptor (BCR) signals are crucial for initiation of humoral immune responses and must be actively modulated and/or terminated in preparation for receipt of subsequent cues for progression. BCR signaling is also actively inhibited in autoreactive cells in which unresponsiveness is maintained by anergy. This serves to prevent cell activation and autoimmunity. Importantly, the feedback mechanisms that modulate and/or terminate signaling during normal antigen-induced B-cell activation appear to also be involved in maintaining B-cell anergy. In fact, it is suggested that anergy reflects nothing more than the normal inability of cells to respond to antigen following preceding stimulation of normal inhibitory feedback mechanisms. Thus, the time-honored two-signal hypothesis is almost certainly correct, with second signals being required to release the cell from inhibitory BCR-specific and trans-active feedback regulation.

References

Mar 1, 1988·Clinical Immunology and Immunopathology·C B WolfowiczA Marshak-Rothstein
Mar 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·G J Nossal, B L Pike
Jan 1, 1994·The Journal of Experimental Medicine·D A Fulcher, A Basten
Dec 16, 1998·The Journal of Biological Chemistry·M J AmanK S Ravichandran
Jun 8, 1999·The Journal of Experimental Medicine·P SchneiderJ Tschopp
Dec 10, 1999·The Journal of Experimental Medicine·F MackayJ L Browning
Oct 24, 2000·Immunological Reviews·A M BrauweilerJ C Cambier
Nov 21, 2000·The Journal of Experimental Medicine·M BattenF Mackay
Apr 12, 2002·Nature·Elizabeth A LeadbetterAnn Marshak-Rothstein
Apr 27, 2002·Nature·Ingrid MecklenbräukerAlexander Tarakhovsky
Jul 3, 2002·The Journal of Experimental Medicine·Takaharu OkadaJason G Cyster
Nov 13, 2002·Annual Review of Immunology·Fabienne MackayJeffrey Browning
Dec 18, 2002·The Journal of Experimental Medicine·Margaret L HibbsDavid M Tarlinton
Aug 16, 2003·Science·Hedda WardemannMichel C Nussenzweig
Nov 25, 2003·Lancet·David C WraithPaul-Henri Lambert
Apr 16, 2004·Cell·Alena M Gallegos, Michael J Bevan
May 25, 2004·Nature Immunology·Regina HalversonRoberta Pelanda
Sep 14, 2004·Nature·Ingrid MecklenbräukerAlexander Tarakhovsky
Sep 28, 2004·Diabetes·F Susan WongMark J Shlomchik
Jul 15, 2005·Annals of the New York Academy of Sciences·Jacques-Olivier PersPierre Youinou
Jul 20, 2005·The Journal of Experimental Medicine·Sean R ChristensenMark J Shlomchik
Aug 30, 2005·Autoimmunity·Vered Molina, Yehuda Shoenfeld

❮ Previous
Next ❯

Citations

Oct 19, 2007·Immunologic Research·Kirthi Raman Kumar, Chandra Mohan
Sep 1, 2007·Current Opinion in Rheumatology·Sergey Yurasov, Michel C Nussenzweig
Apr 5, 2012·Cell Communication and Signaling : CCS·Niklas EngelsJürgen Wienands
Jul 25, 2008·Journal of the American Society of Nephrology : JASN·Donna O BunchPatrick H Nachman
Jul 20, 2010·Immunotherapy·Alexander Link, Martin F Bachmann
Jul 19, 2011·World Journal of Biological Chemistry·Maclean SellarsSusan Chan
Dec 11, 2013·International Immunology·James B Wing, Shimon Sakaguchi
Jan 30, 2014·Immunology Letters·Rochelle M HinmanJohn C Cambier
Jul 12, 2012·Expert Review of Hematology·Maria Teresa Scupoli, Giovanni Pizzolo
May 5, 2007·Expert Opinion on Biological Therapy·Adrienn AngyalGabriella Sármay
Apr 16, 2011·Trends in Immunology·Jarod ZeppXiaoxia Li
May 15, 2007·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Efrat Edry, Doron Melamed
Jan 9, 2009·European Journal of Immunology·Isis Ludwig-PortugallChristian Kurts
Mar 30, 2011·British Journal of Haematology·Nino PorakishviliPeter M Lydyard
Aug 31, 2007·Autoimmunity·Frank J ConradJohn C Cambier
Oct 19, 2017·Nature Reviews. Nephrology·Mia J SmithJohn C Cambier
Sep 27, 2019·Immunological Reviews·Deborah L BurnettChristopher C Goodnow
Jul 3, 2016·Clinical Reviews in Allergy & Immunology·Martin UngererHans-Peter Holthoff
May 14, 2017·Clinical Reviews in Allergy & Immunology·Patrice HemonOlivier Mignen
Aug 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Taras LyubchenkoJohn C Cambier
Jun 3, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Neda NikbakhtTim Manser
Jul 4, 2020·Current Opinion in Endocrinology, Diabetes, and Obesity·Mia J SmithPeter A Gottlieb
Sep 26, 2017·Cerebellum & Ataxias·Hiroshi MitomaChristiane S Hampe
Jun 15, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Natalia V GiltiayXiaoxia Li

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

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.

B cell Activation

B cell activation is initiated by the ligation of the B cell receptor with antigen and ultimately results in the production of protective antibodies against potentially pathogenic invaders. Here is the latest research.