Targeting CD22 with the monoclonal antibody epratuzumab modulates human B-cell maturation and cytokine production in response to Toll-like receptor 7 (TLR7) and B-cell receptor (BCR) signaling

Arthritis Research & Therapy
Natalia V GiltiayEdward A Clark

Abstract

Abnormal B-cell activation is implicated in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). The B-cell surface molecule CD22, which regulates activation through the B-cell receptor (BCR), is a potential target for inhibiting pathogenic B cells; however, the regulatory functions of CD22 remain poorly understood. In this study, we determined how targeting of CD22 with epratuzumab (Emab), a humanized anti-CD22 IgG1 monoclonal antibody, affects the activation of human B-cell subsets in response to Toll-like receptor 7 (TLR7) and BCR engagement. B-cell subsets were isolated from human tonsils and stimulated with F(ab')2 anti-human IgM and/or the TLR7 agonist R848 in the presence of Emab or a human IgG1 isotype control. Changes in mRNA levels of genes associated with B-cell activation and differentiation were analyzed by quantitative PCR. Cytokine production was measured by ELISA. Cell proliferation, survival, and differentiation were assessed by flow cytometry. Pretreatment of phenotypically naïve CD19+CD10-CD27- cells with Emab led to a significant increase in IL-10 expression, and in some but not all patient samples to a reduction of IL-6 production in response to TLR7 stimulation alone or in...Continue Reading

References

Jan 1, 1976·Journal of Immunological Methods·A SaxonR A Robins
Oct 1, 1993·British Journal of Rheumatology·D IsenbergF Stevenson
Jun 1, 1996·Current Opinion in Immunology·G M DoodyD T Fearon
Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·N Razi, A Varki
Sep 12, 2001·The Journal of Biological Chemistry·K L OtipobyE A Clark
Dec 4, 2002·Nature Reviews. Immunology·Hiroaki Niiro, Edward A Clark
Jul 3, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·John P LeonardDavid M Goldenberg
Mar 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Isabelle Béatrice Bekeredjian-DingGunther Hartmann
Mar 26, 2005·Immunological Reviews·Ian R RifkinAnn Marshak-Rothstein
Nov 2, 2005·The Journal of Experimental Medicine·Christina M LauAnn Marshak-Rothstein
May 20, 2006·Science·Prapaporn PisitkunSilvia Bolland
Jul 25, 2006·Arthritis Research & Therapy·Serge D SteinfeldOlivier Pradier
Mar 24, 2007·Nature Reviews. Immunology·Paul R CrockerAjit Varki
May 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chungwen WeiIñaki Sanz
Dec 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vanessa L BryantStuart G Tangye
Dec 11, 2007·Immunology·Jennifer A Walker, Kenneth G C Smith
Feb 9, 2008·Seminars in Immunology·Iñaki SanzJennifer Anolik
Nov 11, 2008·The Journal of Allergy and Clinical Immunology·Mark C GlaumArnold I Levinson
Jan 14, 2009·The Journal of Experimental Medicine·Oliver DienzMercedes Rincon
Aug 25, 2009·Mechanisms of Ageing and Development·Giuseppina Colonna-RomanoCalogero Caruso
Oct 23, 2009·Journal of Autoimmunity·Marie-Laure Santiago-RaberShozo Izui
Dec 1, 2009·Journal of Autoimmunity·Marie-Laure Santiago-RaberShozo Izui
Jul 6, 2010·Journal of Immunological Methods·Thomas DörnerPeter E Lipsky
Aug 25, 2010·Proceedings of the National Academy of Sciences of the United States of America·Nan ShenBetty P Tsao
Sep 3, 2010·European Journal of Immunology·Jean-David BouazizPhilippe Musette
Dec 24, 2010·Journal of Innate Immunity·Norihito KawasakiJames C Paulson
Feb 11, 2011·Seminars in Immunology·Nathaniel M Green, Ann Marshak-Rothstein
Nov 15, 2011·Arthritis Research & Therapy·Thomas DörnerPeter E Lipsky
Dec 2, 2011·The New England Journal of Medicine·George C Tsokos
Mar 22, 2012·Immunologic Research·T CelharA-M Fairhurst
Sep 29, 2012·The Journal of Biological Chemistry·Nathaniel M GreenAnn Marshak-Rothstein
Oct 23, 2012·International Reviews of Immunology·Thomas DörnerKenneth G C Smith
Nov 15, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sun-Hee HwangAnna-Marie Fairhurst

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Citations

Mar 16, 2018·Expert Review of Clinical Immunology·Daniel Geh, Caroline Gordon
Dec 6, 2017·Arthritis & Rheumatology·Sarah Karrar, Deborah S Cunninghame Graham
Oct 4, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kyle J BednarMatthew S Macauley
Sep 4, 2018·Expert Review of Clinical Immunology·Iris L A Bodewes, Marjan A Versnel
Jul 10, 2019·PLoS Biology·Anne M ScottWeiming Li
Jun 6, 2018·Rheumatology International·Konstantinos Melissaropoulos, Stamatis-Nick Liossis
Oct 17, 2018·Frontiers in Immunology·Edward A Clark, Natalia V Giltiay
Nov 11, 2019·Clinical Rheumatology·Qihang YuanJing Wei
May 11, 2021·Clinical and Experimental Immunology·Yuzi LiFanlei Hu
Nov 4, 2021·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Bin WangGuixiu Shi

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Methods Mentioned

BETA
density-gradient centrifugation
flow cytometry
ELISA
glycosylation

Software Mentioned

GraphPad
Prism
FlowJo
IDEAS

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