Siglec-2 Is a Key Molecule for Immune Response
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.
KeywordsSignal Regulation Antigen Stimulation Previous Infection Cell Antigen Receptor Antibody Secreting Cell
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