B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase |
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Authors: | Annaiah Cariappa Hiromu Takematsu Haoyuan Liu Sandra Diaz Khaleda Haider Cristian Boboila Geetika Kalloo Michelle Connole Hai Ning Shi Nissi Varki Ajit Varki and Shiv Pillai |
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Institution: | 1.Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129;2.Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093;3.New England Primate Research Center, Harvard Medical School, Southborough, MA 01772 |
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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. |
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