B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase

Annaiah Cariappa, Hiromu Takematsu, Haoyuan Liu, Sandra Diaz, Khaleda Haider, Cristian Boboila, Geetika Kalloo, Michelle Connole, Hai Ning Shi, Nissi Varki, Ajit Varki, Shiv Pillai

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86 Citations (Scopus)

Abstract

We show that the enzymatic acetylation and deacetylation of a cell surface carbohydrate controls B cell development, signaling, and immunological tolerance. Mice with a mutation in sialate:O-acetyl esterase, an enzyme that specifically removes acetyl moieties from the 9-OH position of α2-6-linked sialic acid, exhibit enhanced B cell receptor (BCR) activation, defects in peripheral B cell development, and spontaneously develop antichromatin autoantibodies and glomerular immune complex deposits. The 9-O-acetylation state of sialic acid regulates the function of CD22, a Siglec that functions in vivo as an inhibitor of BCR signaling. These results describe a novel catalytic regulator of B cell signaling and underscore the crucial role of inhibitory signaling in the maintenance of immunological tolerance in the B lineage.

Original languageEnglish
Pages (from-to)125-138
Number of pages14
JournalJournal of Experimental Medicine
Volume206
Issue number1
DOIs
Publication statusPublished - 16-01-2009

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Cariappa, A., Takematsu, H., Liu, H., Diaz, S., Haider, K., Boboila, C., Kalloo, G., Connole, M., Shi, H. N., Varki, N., Varki, A., & Pillai, S. (2009). B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase. Journal of Experimental Medicine, 206(1), 125-138. https://doi.org/10.1084/jem.20081399