Danzer Claus-Peter, Collins Brian E, Blixt Ola, Paulson James C, Nitschke Lars
Institute of Virology and Immunobiology, University of Würzburg, Versbacherstrasse 7, 97078 Würzburg, Germany.
Int Immunol. 2003 Oct;15(10):1137-47. doi: 10.1093/intimm/dxg114.
CD22, a B cell-specific member of the Siglec family, is an important inhibitor of B cell signaling. The first Ig-like domain of CD22 specifically binds to alpha2,6-linked sialic acids. Through these interactions CD22 can mediate adhesion to other cells in trans, but can also bind endogenous ligands on the B cell surface in cis. Cis binding of CD22 to sialylated ligands enhances the efficiency of inhibition and thereby reduces the BCR signaling strength. In this study we used a newly developed oligomeric streptavidin-based sialylated probe as an artificial CD22 ligand. We found that CD22 is bound to ligands in cis on most B cells. However, there is a proportion of B cells with unbound (unmasked) CD22. The subpopulation with unmasked CD22 is 2-fold increased in transitional and marginal zone B cells in the spleen and on B1 cells in the peritoneum, when compared to mature B cells. Also, B cells with unmasked CD22 have an activated phenotype. Unmasking of CD22 could be functionally involved in lowering the signaling threshold on developmental checkpoints such as transitional B cells and during B cell activation or could be a consequence of such activation processes.
CD22是唾液酸结合免疫球蛋白样凝集素（Siglec）家族的B细胞特异性成员，是B细胞信号传导的重要抑制剂。CD22的第一个免疫球蛋白样结构域特异性结合α2,6连接的唾液酸。通过这些相互作用，CD22可以介导与其他细胞的反式黏附，但也可以在顺式中结合B细胞表面的内源性配体。CD22与唾液酸化配体的顺式结合提高了抑制效率，从而降低了BCR信号强度。在本研究中，我们使用了一种新开发的基于寡聚链霉亲和素的唾液酸化探针作为人工CD22配体。我们发现，在大多数B细胞中，CD22与顺式配体结合。然而，有一部分B细胞的CD22未结合（未被掩盖）。与成熟B细胞相比，脾脏中的过渡性和边缘区B细胞以及腹膜中的B1细胞中未被掩盖的CD22亚群增加了2倍。此外，具有未被掩盖的CD22的B细胞具有活化表型。CD22的去掩盖可能在功能上参与降低发育检查点（如过渡性B细胞）以及B细胞活化期间的信号阈值，或者可能是这种活化过程的结果。
