Antibody repertoires in humanized NOD-scid-IL2Rγ(null) mice and human B cells reveals human-like diversification and tolerance checkpoints in the mouse.

PloS One
Gregory C IppolitoGeorge Georgiou

Abstract

Immunodeficient mice reconstituted with human hematopoietic stem cells enable the in vivo study of human hematopoiesis. In particular, NOD-scid-IL2Rγ(null) engrafted mice have been shown to have reasonable levels of T and B cell repopulation and can mount T-cell dependent responses; however, antigen-specific B-cell responses in this model are generally poor. We explored whether developmental defects in the immunoglobulin gene repertoire might be partly responsible for the low level of antibody responses in this model. Roche 454 sequencing was used to obtain over 685,000 reads from cDNA encoding immunoglobulin heavy (IGH) and light (IGK and IGL) genes isolated from immature, naïve, or total splenic B cells in engrafted NOD-scid-IL2Rγ(null) mice, and compared with over 940,000 reads from peripheral B cells of two healthy volunteers. We find that while naïve B-cell repertoires in humanized mice are chiefly indistinguishable from those in human blood B cells, and display highly correlated patterns of immunoglobulin gene segment use, the complementarity-determining region H3 (CDR-H3) repertoires are nevertheless extremely diverse and are specific for each individual. Despite this diversity, preferential D(H)-J(H) pairings repeatedly...Continue Reading

References

Jan 1, 1984·Annual Review of Biochemistry·D Eisenberg
Sep 29, 1995·Annals of the New York Academy of Sciences·B D Stollar
Feb 1, 1994·Molecular Immunology·E A Padlan
Apr 8, 1998·Immunotechnology : an International Journal of Immunological Engineering·D Sblattero, A Bradbury
Sep 7, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·M I RossiP W Kincade
Sep 19, 2001·The Journal of Clinical Investigation·E MeffreC Schiff
Oct 3, 2001·The Journal of Clinical Investigation·A E Pugh-BernardI Sanz
Aug 16, 2003·Science·Hedda WardemannMichel C Nussenzweig
Jun 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael P Cancro, John F Kearney
Mar 2, 2005·The Journal of Experimental Medicine·Sergey YurasovMichel C Nussenzweig
Mar 8, 2005·Clinical and Experimental Medicine·T Dörner, P E Lipsky
Mar 30, 2005·Journal of Child Neurology·John B Bodensteiner, Stanley D Johnsen
Aug 9, 2005·Developmental and Comparative Immunology·Harry W Schroeder
Oct 8, 2005·The Journal of Clinical Investigation·Amedeo CappioneIñaki Sanz
Feb 24, 2006·Nature Reviews. Immunology·Takashi Nagasawa
Jun 7, 2006·The Journal of Experimental Medicine·Gregory C IppolitoHarry W Schroeder
Jan 30, 2007·Nature Reviews. Immunology·Leonard D ShultzDale L Greiner
Jun 1, 2007·Autoimmunity Reviews·Angela Lee ForemanM Eric Gershwin
Sep 1, 2007·Current Opinion in Rheumatology·Sergey Yurasov, Michel C Nussenzweig
May 6, 2008·Current Opinion in Immunology·Jason E Stadanlick, Michael P Cancro
May 9, 2009·Science·Joshua A WeinsteinStephen R Quake
Sep 22, 2009·Nature Immunology·Markus G Manz, James P Di Santo
Oct 31, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jacob GlanvilleJaume Pons
Apr 7, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tobias RogoschMichael Zemlin

❮ Previous
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Citations

Jan 21, 2014·Nature Biotechnology·George GeorgiouStephen R Quake
Jan 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jason J LavinderGeorge Georgiou
Jun 22, 2014·Journal of Immunological Methods·Julien VillaudyHergen Spits
Jan 22, 2013·Annual Review of Immunology·Anthony RongvauxMarkus G Manz
Jan 22, 2013·Nature Biotechnology·Brandon J DeKoskyGeorge Georgiou
Oct 30, 2013·The Journal of Infectious Diseases·Edward Seung, Andrew M Tager
Feb 6, 2016·Nature Protocols·Jonathan R McDanielGeorge Georgiou
Aug 6, 2013·European Journal of Immunology·Carol LeungChristian Münz
Mar 29, 2014·Frontiers in Immunology·Eva Szymanska MroczekHarry W Schroeder
Apr 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Brandon J DeKoskyGeorge Georgiou
Dec 22, 2016·Nature Communications·Gabriel C WuGregory C Ippolito
Jul 15, 2017·Expert Opinion on Biological Therapy·Ambuj ShrivastavaManmohan Parida
Apr 26, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nancy S LongoPeter E Lipsky
Apr 29, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yanling LiuGötz R A Ehrhardt
Mar 24, 2015·PloS One·Giulia PacielloElisa Ficarra
Dec 30, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Melissa A GawronLisa A Cavacini
Oct 13, 2012·Nature Reviews. Immunology·Leonard D ShultzDale L Greiner
Jun 19, 2019·Bioanalysis·Sophie Tourdot, Timothy P Hickling
Oct 30, 2012·Nature Reviews. Immunology·Oliver Pabst
Dec 24, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michelle L RatliffCarol F Webb
Jul 29, 2020·Viruses·Monika A ZelazowskaLaurie T Krug
Sep 1, 2017·Frontiers in Immunology·Ilja V KhavrutskiiChristopher L Cooper
Mar 24, 2018·Frontiers in Immunology·Sara D'AngeloAndrew R M Bradbury
Mar 11, 2017·Human Vaccines & Immunotherapeutics·J TorresiM Pellegrini
Apr 21, 2021·Molecular Cell·Teresa SadrasMarkus Müschen
Jun 15, 2017·Immunology Letters·Raquel Tayar NogueiraMoriya Tsuji
Jul 2, 2021·The Journal of Clinical Investigation·Jiwon JungGeorge Georgiou

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Datasets Mentioned

BETA
SRA049345.2

Methods Mentioned

BETA
flow cytometry
PCR
454 sequencing

Software Mentioned

Perl scripts
IGKJ
CellQuest
WEASEL
highV
QUEST

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