Regulation of B Cell Functions by the Sialic Acid-Binding Receptors Siglec-G and CD22

Chair of Genetics, University of Erlangen Erlangen, Germany.
Frontiers in Immunology 11/2011; 2:96. DOI: 10.3389/fimmu.2011.00096
Source: PubMed


B cell antigen receptor (BCR) engagement can lead to many different physiologic outcomes. To achieve an appropriate response, the BCR signal is interpreted in the context of other stimuli and several additional receptors on the B cell surface participate in the modulation of the signal. Two members of the Siglec (sialic acid-binding immunoglobulin-like lectin) family, CD22 and Siglec-G have been shown to inhibit the BCR signal. Recent findings indicate that the ability of these two receptors to bind sialic acids might be important to induce tolerance to self-antigens. Sialylated glycans are usually absent on microbes but abundant in higher vertebrates and might therefore provide an important tolerogenic signal. Since the expression of the specific ligands for Siglec-G and CD22 is tightly regulated and since Siglecs are not only able to bind their ligands in trans but also on the same cell surface this might provide additional mechanisms to control the BCR signal. Although both Siglec-G and CD22 are expressed on B cells and are able to inhibit BCR mediated signaling, they also show unique biological functions. While CD22 is the dominant regulator of calcium signaling on conventional B2 cells and also seems to play a role on marginal zone B cells, Siglec-G exerts its function mainly on B1 cells and influences their lifespan and antibody production. Both Siglec-G and CD22 have also recently been linked to toll-like receptor signaling and may provide a link in the regulation of the adaptive and innate immune response of B cells.

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    • "However, it is not known whether macaque CD22 has similar inhibitory functions, carbohydrate binding properties, and involvement in TLR-signaling as has been reported for human and mouse B-cells [139]. In addition human B-cells express Siglec-5, 6, 9 and 10 [139] which as members of the CD33-related group have been shown to evolve more rapidly than CD22 [137], and may also differ in the rhesus macaque. The extent to which potential siglec differences impact B cell regulation in the macaque should be explored to fully elucidate B cell maturation and development and take full advantage of the NHP model. "
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    • "In terms of Siglec-10, it is likely that CLL cells also express this protein because it is expressed on CD5+ B cells [112] from which CLL cells are reported to derive [113]. Both CD22 and Siglec-10 are involved in maintaining B cell tolerance and associate with the BCR to regulate Ca2+ release during its engagement [114]. It is therefore tempting to speculate that high levels of CD22 and Siglec-10 on CLL cells may have a role in maintaining tolerance within anergised cells. "
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    ABSTRACT: Chronic lymphocytic leukaemia (CLL) is an incurable malignancy of mature B cells. CLL is important clinically in Western countries because of its commonality and because of the significant morbidity and mortality associated with the progressive form of this incurable disease. The B cell receptor (BCR) expressed on the malignant cells in CLL contributes to disease pathogenesis by providing signals for survival and proliferation, and the signal transduction pathway initiated by engagement of this receptor is now the target of several therapeutic strategies. The purpose of this review is to outline current understanding of the BCR signal cascade in normal B cells and then question whether this understanding applies to CLL cells. In particular, this review studies the phenomenon of anergy in CLL cells, and whether certain adaptations allow the cells to overcome anergy and allow full BCR signaling to take place. Finally, this review analyzes how BCR signals can be therapeutically targeted for the treatment of CLL.
    07/2014; 2014:208928. DOI:10.1155/2014/208928
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    ABSTRACT: CD22 is a 140-kDa member of the Siglec family of cell surface proteins that is expressed by most mature B-cell lineages. As a co-receptor of the B-cell receptor (BCR), it is known to contribute to the sensitive control of the B-cell response to antigen. Cross-linking of CD22 and the BCR by antigen triggers the phosphorylation of CD22, which leads to activation of signaling molecules such as phosphatases. Signal transduction pathways involving CD22 have been explored in a number of mouse models, some of which have provided evidence that in the absence of functional CD22, B cells have a "hyperactivated" phenotype, and suggest that loss of CD22 function could contribute to the pathogenesis of autoimmune diseases. Modulating CD22 activity has therefore been suggested as a possible therapeutic approach to such diseases. For example, the novel CD22-targeting monoclonal antibody epratuzumab is currently under investigation as a treatment for the connective tissue disorder systemic lupus erythematosus (SLE).
    International Reviews Of Immunology 10/2012; 31(5):363-78. DOI:10.3109/08830185.2012.709890 · 4.10 Impact Factor
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