Sialylated multivalent antigens engage CD22 in trans and inhibit B cell activation
Sialylated multivalent antigens engage CD22 in trans and inhibit B cell activation
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DOI：
10.1073/pnas.0807207106
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发表时间：
2009-02-24
影响因子：
11.1
通讯作者：
Kiessling, Laura L.
中科院分区：
文献类型：
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作者：
Courtney, Adam H.;Puffer, Erik B.;Kiessling, Laura L.
CD 22是B细胞表面上的抑制性辅助受体，其减弱B细胞抗原受体（BCR）信号传导，并因此减弱B细胞活化。阐明CD22抑制活性的分子机制由于CD22配体的普遍存在而变得复杂。虽然抗原可以展示CD22配体，但已知该受体结合细胞表面上的唾液酸化糖蛋白。CD22和细胞表面糖蛋白配体的接近性导致了受体的抑制特性是由于顺式相互作用的结论。在这里，我们研究的功能后果的反式相互作用，采用唾液酸化的多价抗原，可以从事CD22和BCR。将B细胞暴露于唾液酸化抗原导致BCR信号传导中的关键步骤受到抑制。这些结果表明，带有CD 22配体的抗原是B细胞活化的强有力抑制剂。唾液酸化抗原通过反式CD22相互作用抑制BCR信号传导的能力揭示了Siglec受体家族作为免疫信号传导调节剂的先前未被认识的作用。
CD22 is an inhibitory coreceptor on the surface of B cells that attenuates B cell antigen receptor (BCR) signaling and, therefore, B cell activation. Elucidating the molecular mechanisms underlying the inhibitory activity of CD22 is complicated by the ubiquity of CD22 ligands. Although antigens can display CD22 ligands, the receptor is known to bind to sialylated glycoproteins on the cell surface. The propinquity of CD22 and cell-surface glycoprotein ligands has led to the conclusion that the inhibitory properties of the receptor are due to cis interactions. Here, we examine the functional consequences of trans interactions by employing sialylated multivalent antigens that can engage both CD22 and the BCR. Exposure of B cells to sialylated antigens results in the inhibition of key steps in BCR signaling. These results reveal that antigens bearing CD22 ligands are powerful suppressors of B cell activation. The ability of sialylated antigens to inhibit BCR signaling through trans CD22 interactions reveals a previously unrecognized role for the Siglec-family of receptors as modulators of immune signaling.