Cutting edge: The PTPN22 allelic variant associated with autoimmunity impairs B cell signaling

Adrian F. Arechiga, Tania Habib, Yantao He, Xian Zhang, Zhong Yin Zhang, Andrew Funk, Jane H. Buckner

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

PTPN22 is a gene encoding the protein tyrosine phosphatase Lyp. A missense mutation changing residue 1858 from cytosine to thymidine (1858C/T) is associated with multiple autoimmune disorders. Studies have demonstrated that Lyp has an inhibitory effect on TCR signaling; however, the presence of autoantibodies in all of the diseases associated with the 1858T variant and recent evidence that Ca2+ flux is altered in B cells of 1858T carriers indicate a role for Lyp in B cell signaling. In this study we show that B cell signal transduction is impaired in individuals who express the variant. This defect in signaling is characterized by a deficit in proliferation, a decrease in phosphorylation of key signaling proteins, and is reversed by inhibition of Lyp. These findings suggest that the PTPN22 1858T variant alters BCR signaling and implicate B cells in the mechanism by which the PTPN22 1858T variant contributes to autoimmunity.

Original languageEnglish (US)
Pages (from-to)3343-3347
Number of pages5
JournalJournal of Immunology
Volume182
Issue number6
DOIs
StatePublished - Mar 15 2009

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Autoimmunity
B-Lymphocytes
Non-Receptor Type 22 Protein Tyrosine Phosphatase
Cytosine
Missense Mutation
Autoantibodies
Thymidine
Signal Transduction
Proteins
Phosphorylation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Cutting edge : The PTPN22 allelic variant associated with autoimmunity impairs B cell signaling. / Arechiga, Adrian F.; Habib, Tania; He, Yantao; Zhang, Xian; Zhang, Zhong Yin; Funk, Andrew; Buckner, Jane H.

In: Journal of Immunology, Vol. 182, No. 6, 15.03.2009, p. 3343-3347.

Research output: Contribution to journalArticle

Arechiga, Adrian F. ; Habib, Tania ; He, Yantao ; Zhang, Xian ; Zhang, Zhong Yin ; Funk, Andrew ; Buckner, Jane H. / Cutting edge : The PTPN22 allelic variant associated with autoimmunity impairs B cell signaling. In: Journal of Immunology. 2009 ; Vol. 182, No. 6. pp. 3343-3347.
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