Sialic Acid Binding Domains of CD22 Are Required For Negative Regulation of B Cell Receptor Signaling

doi:10.1084/jem.20011796

Published online 29 April 2002 doi:10.1084/jem.20011796

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© Rockefeller University Press, 0022-1007/2002/5/1199/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 9, May 6, 2002 1199-1205

Brief Definitive Report

Sialic Acid Binding Domains of CD22 Are Required For Negative Regulation of B Cell Receptor Signaling

Lei Jin², Paul A. McLean¹, Benjamin G. Neel³ and Henry H. Wortis¹^,2

¹ Department of Pathology, Tufts University School of Medicine and Sackler School of Graduate Biomedical Sciences, Boston, MA 02111
² Program in Genetics, Tufts University School of Medicine and Sackler School of Graduate Biomedical Sciences, Boston, MA 02111
³ Cancer Biology Program, Division of Hematology-Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215

Address correspondence to Henry H. Wortis, Dept. of Pathology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111. Phone: 617-636-6718; Fax: 617-636-2990; E-mail: henry.wortis{at}tufts.edu

CD22, a negative regulator of B cell antigen receptor signaling,binds glycoconjugates terminating in ${alpha}$ 2, 6 sialic acid. The physiologicalligand(s) for CD22 remain unknown. We asked whether the sialicacid binding domains are necessary for CD22 to function as anegative regulator. We generated two mutants that lack sialicacid binding activity and expressed them in a novel CD22^-/-murine B cell line. Anti-IgM activated B cells expressing eitherCD22 mutant had greater Ca²⁺ responses than cells expressingwild-type CD22. Each variant also had reduced CD22 tyrosinephosphorylation and Src homology 2 domain–containing proteintyrosine phosphatase-1 association. These data suggest thatthe ${alpha}$ 2, 6 sialic acid ligand binding activity of CD22 is criticalfor its negative regulatory functions.

Key Words: signal transduction • SHP-1 • calcium • siglec • tyrosine phosphorylation

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