PT  - JOURNAL ARTICLE
AU  - Arechiga, Adrian F.
AU  - Habib, Tania
AU  - He, Yantao
AU  - Zhang, Xian
AU  - Zhang, Zhong-Yin
AU  - Funk, Andrew
AU  - Buckner, Jane H.
TI  - Cutting Edge: The PTPN22 Allelic Variant Associated with Autoimmunity Impairs B Cell Signaling
AID  - 10.4049/jimmunol.0713370
DP  - 2009 Mar 15
TA  - The Journal of Immunology
PG  - 3343--3347
VI  - 182
IP  - 6
4099  - http://www.jimmunol.org/content/182/6/3343.short
4100  - http://www.jimmunol.org/content/182/6/3343.full
SO  - J. Immunol.2009 Mar 15; 182
AB  - 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.