The Journal of Experimental Medicine
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doi:10.1084/jem.20081399
The Journal of Experimental Medicine
The Rockefeller University Press, 0022-1007 $30.00
© Cariappa et al.
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ARTICLE

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

Annaiah Cariappa1, Hiromu Takematsu2, Haoyuan Liu1, Sandra Diaz2, Khaleda Haider1, Cristian Boboila1, Geetika Kalloo1, Michelle Connole3, Hai Ning Shi1, Nissi Varki2, Ajit Varki2, and Shiv Pillai1

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

CORRESPONDENCE Shiv Pillai: pillai{at}helix.mgh.harvard.edu

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 {alpha}2–6-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.

Abbreviations used: BCR, B cell receptor; CMAH, CMP-Neu-5Ac hydroxylase; ES, embryonic stem; ITIM, immunoreceptor tyrosine-based inhibitory motif; MZ, marginal zone; MZP, marginal zone B cell precurso; Siae: sialic acid acetyl esterase.

H. Takematsu's present address is Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.

© 2009 Cariappa et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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