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Siglec-2 Is a Key Molecule for Immune Response

  • Takeshi Tsubata

Abstract

Siglecs are sialic acid-binding membrane-bound lectins expressed on various hematopoietic cells (Varki and Angata 2006). Siglec-2 (also called as CD22) specifically recognizes α2.6 sialic acid-containing glycans and is expressed on B cells, the precursors of antibody secreting cells, plasma cells (Nitschke and Tsubata 2004). Both biochemical analysis on various B cells and studies using Siglec-2-deficient mice have demonstrated that Siglec-2 negatively regulates signaling through the B cell antigen receptor (BCR), which plays a crucial role in response of B cells to antigen stimulation. B cells express membrane-bound immunoglobulin (Ig) as BCR. Ligation of BCR by antigens activates BCR-associated kinases, which in turn phosphorylate various substrates, leading to activation of various signaling cascades including Ca2+ signaling. Siglec-2 negatively regulates BCR signaling by recruitment and activation of SH2-containing phosphatase 1 (SHP-1), which counteracts the phospharylation-mediated activation of signaling molecules by dephosphorylation, and reduces Ca2+ signaling by regulating the activity of the Ca2+ pump PMCA. In the past few years, we have assessed the immunological function of Siglec-2 and found that it functions as a molecular switch that determines the fate of antigen-interacted B cells whether they undergo apoptosis or activation. Siglec-2 may therefore play a key role in the establishment and maintenance of normal humoral immunity, which produces antibodies to pathogens but not self-antigens, and, after vaccination, respond to pathogens rapidly.

Keywords

Signal Regulation Antigen Stimulation Previous Infection Cell Antigen Receptor Antibody Secreting Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2008

Authors and Affiliations

  • Takeshi Tsubata
    • 1
  1. 1.Laboratory of Immunology, School of Biomedical ScienceTokyo Medical and Dental University; CREST, JSTTokyoJapan

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