Self-reactive VH4-34-expressing IgG B cells recognize commensal bacteria

The Journal of Experimental Medicine
Jean-Nicolas SchickelE Meffre

Abstract

The germline immunoglobulin (Ig) variable heavy chain 4-34 (VH4-34) gene segment encodes in humans intrinsically self-reactive antibodies that recognize I/i carbohydrates expressed by erythrocytes with a specific motif in their framework region 1 (FWR1). VH4-34-expressing clones are common in the naive B cell repertoire but are rarely found in IgG memory B cells from healthy individuals. In contrast, CD27(+)IgG(+) B cells from patients genetically deficient for IRAK4 or MYD88, which mediate the function of Toll-like receptors (TLRs) except TLR3, contained VH4-34-expressing clones and showed decreased somatic hypermutation frequencies. In addition, VH4-34-encoded IgGs from IRAK4- and MYD88-deficient patients often displayed an unmutated FWR1 motif, revealing that these antibodies still recognize I/i antigens, whereas their healthy donor counterparts harbored FWR1 mutations abolishing self-reactivity. However, this paradoxical self-reactivity correlated with these VH4-34-encoded IgG clones binding commensal bacteria antigens. Hence, B cells expressing germline-encoded self-reactive VH4-34 antibodies may represent an innate-like B cell population specialized in the containment of commensal bacteria when gut barriers are breached.

References

Dec 1, 1996·Alimentary Pharmacology & Therapeutics·C D Settle, M H Wilcox
Sep 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kathleen N PotterBrian J Sutton
Mar 15, 2003·Science·Capucine PicardJean-Laurent Casanova
Aug 16, 2003·Science·Hedda WardemannMichel C Nussenzweig
Apr 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eric H EklandJason G Cyster
Aug 18, 2004·Current Opinion in Rheumatology·Jennifer Anolik, Iñaki Sanz
Sep 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bing HeAndrea Cerutti
Oct 8, 2005·The Journal of Clinical Investigation·Amedeo CappioneIñaki Sanz
Feb 20, 2007·Immunity·Thomas TillerHedda Wardemann
Aug 2, 2008·Science·Horst von BernuthJean-Laurent Casanova
Oct 16, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Séverine BoullierArmelle Phalipon
Jul 21, 2010·Nature Immunology·Christopher C GoodnowRobert Brink
Jan 12, 2011·Annual Review of Immunology·Jean-Laurent CasanovaLluis Quintana-Murci
Jan 12, 2011·The Journal of Experimental Medicine·Jens WrammertPatrick C Wilson
Apr 15, 2011·The Journal of Clinical Investigation·Julia BenckertHedda Wardemann
Aug 2, 2011·The Journal of Clinical Investigation·Laurence MenardEric Meffre
Oct 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Johannes F ScheidHedda Wardemann
Jan 10, 2012·Annual Review of Immunology·Gabriel D Victora, Michel C Nussenzweig
Sep 21, 2013·The Journal of Clinical Investigation·Neil RombergEric Meffre
May 14, 2014·Proceedings of the National Academy of Sciences of the United States of America·Zahra SabouriChristopher C Goodnow
Sep 26, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chetna SoniZiaur S M Rahman
Oct 2, 2014·MBio·Arancha HeviaAbelardo Margolles
Oct 17, 2014·Blood·Paul J MaglioneCharlotte Cunningham-Rundles
Jul 8, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Magdalena A BerkowskaMenno C van Zelm
Oct 21, 2015·Proceedings of the National Academy of Sciences of the United States of America·Ryan M YoungLouis M Staudt
Jun 15, 2016·The Journal of Experimental Medicine·Joanne H ReedChristopher C Goodnow

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Citations

Mar 27, 2018·Immunology·Rachael J M Bashford-RogersDavid C Thomas
Apr 29, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yanling LiuGötz R A Ehrhardt
Jan 10, 2019·Current Opinion in Rheumatology·Carina DehnerMartin A Kriegel
Mar 8, 2019·Annals of Neurology·Nina Kerstin WenkeHarald Prüss
Nov 21, 2018·Journal of Leukocyte Biology·Sandra Romero-RamírezJosé L Maravillas-Montero
Sep 27, 2019·Nature·R J M Bashford-RogersK G C Smith
May 1, 2019·Nature Communications·Marion EspéliKenneth G C Smith
Dec 17, 2019·The Journal of Experimental Medicine·Anthony LauElissa K Deenick
Sep 29, 2019·Immunological Reviews·Joel FinneyMasayuki Kuraoka
May 18, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Takuya NojimaMasayuki Kuraoka
Aug 14, 2019·Immunological Reviews·Silvia PreitePamela L Schwartzberg
Jun 6, 2018·Frontiers in Immunology·Gregory J Tsay, Moncef Zouali
Jul 6, 2018·Frontiers in Immunology·Jincy M IssacBasel K Al-Ramadi
Jan 11, 2020·Frontiers in Immunology·Jessica D Gereige, Paul J Maglione
Jan 19, 2020·Scientific Reports·Esther Veronika WenzelMichael Hust
Aug 28, 2020·Frontiers in Immunology·Marie GhraichyJohannes Trück
Dec 18, 2020·Immunology Letters·Suran L FernandoJamma Li
Dec 20, 2020·Nature Reviews. Rheumatology·Simon FillatreauThomas Dörner
Oct 8, 2018·Current Opinion in Immunology·Mark Noviski, Julie Zikherman
May 13, 2021·Nature Reviews. Immunology·Harald Prüss

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Methods Mentioned

BETA
ELISA
glycosylation
PCR
ELISAs

Software Mentioned

IGBLAST

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