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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 2, 6 sialic acid. The physiological ligand(s) for CD22 remain unknown. We asked whether the sialic acid binding domains are necessary for CD22 to function as a negative regulator. We generated two mutants that lack sialic acid binding activity and expressed them in a novel CD22^-/- murine B cell line. Anti-IgM activated B cells expressing either CD22 mutant had greater Ca²⁺ responses than cells expressing wild-type CD22. Each variant also had reduced CD22 tyrosine phosphorylation and Src homology 2 domain–containing protein tyrosine phosphatase-1 association. These data suggest that the 2, 6 sialic acid ligand binding activity of CD22 is critical for its negative regulatory functions.

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

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