Sialic acid binding domains of CD22 are required for negative regulation of B cell receptor signaling.
CD22, a negative regulator of B cell antigen receptor signaling, binds glycoconjugates terminating in alpha2, 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 Ca(2+) 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 alpha2, 6 sialic acid ligand binding activity of CD22 is critical for its negative regulatory functions.
Jin
Lei
L
Department of Pathology, Tufts University School of Medicine and Sackler School of Graduate Biomedical Sciences, Boston, MA 02111, USA.
McLean
Paul A
PA
Neel
Benjamin G
BG
Wortis
Henry H
HH
D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites; D020013:Calcium Signaling / Q000502:physiology*; D015815:Cell Adhesion Molecules; D002460:Cell Line; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000276:immunology; D005822:Genetic Vectors; D006801:Humans; D037102:Lectins; D051379:Mice; D016297:Mutagenesis, Site-Directed; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2; D019158:N-Acetylneuraminic Acid