Phosphotyrosine‐dependent association between CD22 and protein tyrosine phosphatase 1C

Campbell, Mary-Ann

doi:10.1002/eji.1830250616

Cited by 111 publications

(45 citation statements)

References 64 publications

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“…7A). Tyrosine-phosphorylated CD22 recruits SHP-1 phosphatase, a negative regulator of B cell activation (61)(62)(63). However, SA-C3dg binding at concentrations of both 1 and 50 g/ml reduced SHP-1 associations with CD22 by 3 min after BCR ligation (Fig.…”

Section: C3dg Regulation Of Cd22 Phosphorylationmentioning

confidence: 93%

Complement Component C3d-Antigen Complexes Can Either Augment or Inhibit B Lymphocyte Activation and Humoral Immunity in Mice Depending on the Degree of CD21/CD19 Complex Engagement

Lee

Haas

Gor

et al. 2005

The Journal of Immunology

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C3d can function as a molecular adjuvant by binding CD21 and thereby enhancing B cell activation and humoral immune responses. However, recent studies suggest both positive and negative roles for C3d and the CD19/CD21 signaling complex in regulating humoral immunity. To address whether signaling through the CD19/CD21 complex can negatively regulate B cell function when engaged by physiological ligands, diphtheria toxin (DT)-C3d fusion protein and C3dg-streptavidin (SA) complexes were used to assess the role of CD21 during BCR-induced activation and in vivo immune responses. Immunization of mice with DT-C3d3 significantly reduced DT-specific Ab responses independently of CD21 expression or signaling. By contrast, SA-C3dg tetramers dramatically enhanced anti-SA responses when used at low doses, whereas 10-fold higher doses did not augment immune responses, except in CD21/35-deficient mice. Likewise, SA-C3dg (1 μg/ml) dramatically enhanced BCR-induced intracellular calcium concentration ([Ca2+]i) responses in vitro, but had no effect or inhibited [Ca2+]i responses when used at 10- to 50-fold higher concentrations. SA-C3dg enhancement of BCR-induced [Ca2+]i responses required CD21 and CD19 expression and resulted in significantly enhanced CD19 and Lyn phosphorylation, with enhanced Lyn/CD19 associations. BCR-induced CD22 phosphorylation and Src homology 2 domain-containing protein tyrosine phosphatase-1/CD22 associations were also reduced, suggesting abrogation of negative regulatory signaling. By contrast, CD19/CD21 ligation using higher concentrations of SA-C3dg significantly inhibited BCR-induced [Ca2+]i responses and inhibited CD19, Lyn, CD22, and Syk phosphorylation. Therefore, C3d may enhance or inhibit Ag-specific humoral immune responses through both CD21-dependent and -independent mechanisms depending on the concentration and nature of the Ag-C3d complexes.

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Section: C3dg Regulation Of Cd22 Phosphorylationmentioning

confidence: 93%

Complement Component C3d-Antigen Complexes Can Either Augment or Inhibit B Lymphocyte Activation and Humoral Immunity in Mice Depending on the Degree of CD21/CD19 Complex Engagement

Lee

Haas

Gor

et al. 2005

The Journal of Immunology

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“…ST6Gal-deficient B lymphocytes were next analyzed for their ability to accumulate phosphotyrosine on cellular proteins in response to anti-IgM stimulation. CD22 is among those proteins phosphorylated on tyrosine following B cell antigen-receptor activation, and this phosphorylation is reported to recruit the SHP tyrosine phosphatase and other effector molecules to the antigen-receptor complex by SH2 binding interactions (40,41). Phosphotyrosine accumulation on CD22 was observed following anti-IgM stimulation of ST6Gal-deficient B cells (data not shown); however, reduced levels of cell surface CD22 (Fig.…”

Section: St6galmentioning

confidence: 99%

Immune regulation by the ST6Gal sialyltransferase

Hennet

Chui

Paulson

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

330

293

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The ST6Gal sialyltransferase controls production of the Sia␣2-6Gal␤1-4GlcNAc (Sia6LacNAc) trisaccharide, which is the ligand for the lectin CD22. Binding of CD22 to Sia6LacNAc is implicated in regulating lymphocyte adhesion and activation. We have investigated mice that lack ST6Gal and report that they are viable, yet exhibit hallmarks of severe immunosuppression unlike CD22-deficient mice. Notably, Sia6LacNAc-deficient mice display reduced serum IgM levels, impaired B cell proliferation in response to IgM and CD40 crosslinking, and attenuated antibody production to Tindependent and T-dependent antigens. Deficiency of ST6Gal was further found to alter phosphotyrosine accumulation during signal transduction from the B lymphocyte antigen receptor. These studies reveal that the ST6Gal sialyltransferase and corresponding production of the Sia6LacNAc oligosaccharide are essential in promoting B lymphocyte activation and immune function.Sialyltransferases are a family of glycosyltransferase enzymes that add sialic acid residues during oligosaccharide diversification (reviewed in ref. 1). Sialic acid addition occurs in the Golgi apparatus and generally terminates further oligosaccharide chain elongation. The outer position of sialic acid linkages places these residues in a location to provide key structural determinants in ligand formation for endogenous and pathogenic lectins. Three sialic acid linkage types commonly exist among vertebrates and the corresponding sialyltransferase genes have been previously isolated. The most abundant sialic acid linkage found among mammalian cell surface oligosaccharides is of the ␣2-3 variety and can be produced independently by four sialyltransferases that each, nonetheless, bear unique substrate preferences among glycolipids, asparagine (N)-linked glycans, and serine͞threonine (O)-linked glycans (2). Sialyltransferases have also been found to be developmentally regulated and differentially expressed among various cell types (1-6). For example, expression of ␣2-8 linked sialic acids is much less common than ␣2-3 linkages and appears restricted to a small subset of glycoproteins (7-10).␣2-6-linked sialic acids are also less abundant than ␣2-3-linked forms and are generated by at least four distinct gene products. However, the ST6Gal sialyltransferase appears solely responsible for producing the Sia␣2-6Gal␤1-4GlcNAc (Sia6LacNAc) terminus on various N glycans, and perhaps on some O glycans (1, 11). High levels of ST6Gal RNA have been found to preferentially accumulate in hematopoietic cells, as well as in the liver (3-5). Moreover, ST6Gal gene transcription is regulated by multiple promoters and altered by glucocorticoids and cytokines (12)(13)(14). Although the physiologic role of the ST6Gal sialyltransferase has not been defined previously by available genetic approaches, it has been shown to be unique in producing the ligand for the CD22 lectin molecule expressed on B lymphocytes.CD22 is a transmembrane glycoprotein lectin found exclusively on B lymphocytes and is known to p...

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“…Following BCR cross-linking, the Src homology protein 1 tyrosine phosphatase associates with tyrosinephosphorylated CD22, which induces Src homology protein 1 phosphatase activity (22)(23)(24). This results in suppression of mitogen-activated protein kinase activation and counterregulation of CD19 effects (25).…”

mentioning

confidence: 99%

CD19 Signaling Pathways Play a Major Role for Murine AIDS Induction and Progression

Knoetig

Torrey

Naghashfar

et al. 2002

The Journal of Immunology

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Infection of genetically susceptible mice with the LP-BM5 mixture of murine leukemia viruses including an etiologic defective virus (BM5def) causes an immunodeficiency syndrome called murine AIDS (MAIDS). The disease is characterized by interactions between B cells and CD4+ T cells resulting in polyclonal activation of both cell types. It is known that BM5def is expressed at highest levels in B cells and that B cells serve as viral APC. The CD19-CD21 complex and CD22 on the surface of B cells play critical roles as regulators of B cell responses to a variety of stimuli, influencing cell activation, differentiation, and survival. CD19 integrates positive signals induced by B cell receptor ligation by interacting with the protooncogene Vav, which leads to subsequent tyrosine phosphorylation of this molecule. In contrast, CD22 negatively regulates Vav phosphorylation. To analyze the role of CD19, CD21, Vav, and CD22 in MAIDS, we infected mice deficient in CD19, CD21 (CR2), Vav-1, or CD22 with LP-BM5 murine leukemia viruses. Infected CR2−/− mice developed MAIDS with a time course and severity indistinguishable from that of wild-type mice. In contrast, CD19 as well as Vav-1 deficiency restricted viral replication and suppressed the development of typical signs of MAIDS including splenomegaly, lymphadenopathy, and hypergammaglobulinemia. Finally, CD22 deficiency was found to accelerate MAIDS development. These results provide novel insights into the B cell signaling pathways required for normal induction and progression of MAIDS.

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Phosphotyrosine‐dependent association between CD22 and protein tyrosine phosphatase 1C

Cited by 111 publications

References 64 publications

Complement Component C3d-Antigen Complexes Can Either Augment or Inhibit B Lymphocyte Activation and Humoral Immunity in Mice Depending on the Degree of CD21/CD19 Complex Engagement

Complement Component C3d-Antigen Complexes Can Either Augment or Inhibit B Lymphocyte Activation and Humoral Immunity in Mice Depending on the Degree of CD21/CD19 Complex Engagement

Immune regulation by the ST6Gal sialyltransferase

CD19 Signaling Pathways Play a Major Role for Murine AIDS Induction and Progression

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