Defects in Germinal Center Selection in SLE

Frontiers in Immunology
Megan WoodsAnne Davidson

Abstract

Germinal centers (GCs) are the primary site at which clonal expansion and affinity maturation of B cells occur. B cells encounter antigen and receive T cell help in the GC light zone (LZ) and then migrate to the dark zone where they proliferate and undergo somatic mutation before cycling back to the LZ for further rounds of selection. Tolerance to autoantigens is frequently lost de novo as GC B cells undergo class switching and somatic mutation. This loss of tolerance is regulated by a variety of mechanisms including cell death, failure to compete for T cell help, and failure to differentiate into effector cells. Systemic lupus erythematosus (SLE) is characterized by loss of tolerance to nucleic acid antigens. While defects in tolerance occur in the naïve repertoire of SLE patients, pathogenic autoantibodies also arise in the GC by somatic mutation from non-autoreactive precursors. Several B cell defects contribute to the loss of GC tolerance in SLE, including polymorphisms of genes encoded by the Sle1 locus, excess TLR7 signaling, defects in FcRIIB expression, or defects of B cell apoptosis. Extrinsic soluble factors, such as Type-1 IFN and B cell-activating factor, or an increased number of T follicular helper cells in the GC...Continue Reading

References

Apr 1, 1993·The Journal of Experimental Medicine·M Z RadicM Weigert
Mar 5, 1996·Proceedings of the National Academy of Sciences of the United States of America·S K RayB Diamond
Feb 2, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaobo WangAnne Davidson
Dec 18, 2002·The Journal of Experimental Medicine·Yijin LiMartin Weigert
Aug 16, 2003·Science·Hedda WardemannMichel C Nussenzweig
Oct 15, 2003·The Journal of Experimental Medicine·Ziaur S M RahmanTim Manser
Jan 22, 2004·International Immunology·Elahna PaulMichael C Carroll
Aug 10, 2004·Nature Immunology·Christopher D C AllenJason G Cyster
Dec 22, 2004·Springer Seminars in Immunopathology·Jessica J MansonMichael R Ehrenstein
Mar 2, 2005·The Journal of Experimental Medicine·Sergey YurasovMichel C Nussenzweig
Oct 8, 2005·The Journal of Clinical Investigation·Amedeo CappioneIñaki Sanz
Jun 17, 2006·Proceedings of the National Academy of Sciences of the United States of America·Srividya SubramanianEdward K Wakeland
Aug 23, 2006·The Journal of Experimental Medicine·Meggan MackayBetty Diamond
Dec 23, 2006·Science·Christopher D C AllenJason G Cyster
Feb 3, 2007·Nature·Tanja A SchwickertMichel C Nussenzweig
Feb 6, 2007·Seminars in Immunology·Sean R Christensen, Mark J Shlomchik
Feb 20, 2007·Immunity·Thomas TillerHedda Wardemann
Jul 17, 2007·Cell·Christopher C Goodnow
Aug 1, 2007·The Journal of Experimental Medicine·Joanna R GroomFabienne Mackay
Mar 15, 2008·The Journal of Clinical Investigation·Donna L ThibaultPaul J Utz
Jul 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Brun MietznerMichel C Nussenzweig
Oct 11, 2008·Science·Kajsa WingShimon Sakaguchi
Nov 5, 2008·The Journal of Experimental Medicine·Jared M OdegardJoe Craft
Jan 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jason A BubierDerry C Roopenian
Jun 13, 2009·Nature Reviews. Immunology·Fabienne Mackay, Pascal Schneider
Jul 15, 2009·Nature·João P PereiraJason G Cyster
Oct 16, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Raja VuyyuruZiaur S M Rahman
Dec 2, 2009·Nature Reviews. Rheumatology·Anne Davidson, Cynthia Aranow
Dec 18, 2009·Nature Immunology·Kajsa Wing, Shimon Sakaguchi
Apr 27, 2010·Trends in Immunology·Mohey Eldin M El ShikhJohn G Tew
Jul 14, 2010·The Journal of Experimental Medicine·Patrizia ScapiniClifford A Lowell
Jul 21, 2010·Nature Immunology·Christopher C GoodnowRobert Brink
Oct 19, 2010·Arthritis and Rheumatism·Zheng LiuAnne Davidson
Jul 29, 2011·Nature·Changlu LiuTimothy W Lovenberg
Jul 29, 2011·Nature·Sébastien HannedoucheAndreas W Sailer
Oct 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Johannes F ScheidHedda Wardemann

❮ Previous
Next ❯

Citations

Sep 8, 2016·European Journal of Immunology·Benoit DesnuesLena Alexopoulou
Aug 27, 2016·Immunology and Cell Biology·Anthony L DeFranco
Dec 6, 2017·Arthritis & Rheumatology·Sarah Karrar, Deborah S Cunninghame Graham
Nov 1, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robert K AbbottMichail Sitkovsky
Sep 27, 2019·Immunological Reviews·Deborah L BurnettChristopher C Goodnow
Mar 22, 2018·Frontiers in Immunology·Cynthia LouisIan Wicks
Jan 4, 2016·Antibodies·Barbara Dema, Nicolas Charles
Nov 10, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephanie L SchellZiaur S M Rahman
Mar 21, 2018·Frontiers in Immunology·Susan MalkielBetty Diamond
Sep 11, 2019·Rheumatology·Mark N Lazarus
Feb 2, 2021·Frontiers in Immunology·Maria A Bacalao, Anne B Satterthwaite
Aug 3, 2021·Frontiers in Immunology·Sean Robinson, Ranjeny Thomas

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic

Related Concepts

Related Feeds

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.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis