The protein tyrosine phosphatase CD45 plays a crucial role in B cell antigen receptor (BCR) signaling by activating Src family kinases. Cd45^−/− mice show altered B cell development and a phenotype likely due to reduced steady-state signaling; however, Cd45^−/− B cells show relatively normal BCR ligation–induced signaling. In our investigation of how BCR signaling was restored in Cd45^−/− cells, we found that the coreceptor CD22 switched from an inhibitory to a stimulatory function in these cells. We disrupted the ability of CD22 to interact with its ligands in Cd45^−/− B cells by generating Cd45^−/−St6galI^−/− mice, which cannot synthesize the glycan ligand of CD22, or by treating Cd45^−/− B cells in vitro with the sialoside GSC718, which inhibits ligand binding to CD22. BCR ligation–induced signaling was reduced by ST6GalI deficiency, but not by GSC718 treatment, suggesting that CD22 restored BCR ligation–induced signaling in Cd45^−/− mature B cells by altering cellular phenotypes during development. CD22 was required for the increase in the surface amount of IgM-BCR on Cd45^−/− B cells, which augmented signaling. Because B cell survival depends on steady-state BCR signaling, IgM-BCR abundance was likely increased by the selective survival of IgM-BCR^hi Cd45^−/− B cells because of CD22-mediated signaling under conditions of substantially reduced steady-state signaling. Because the amount of surface IgM-BCR is increased on B cells from patients with other BCR signaling deficiencies, including X-linked agammaglobulinemia, our findings suggest that CD22 may contribute to the partial restoration of B cell function in these patients.

The asymmetric unit of the title compound, C 25 H 21 N 3 O 2 S, comprises four molecules. Their conformations differ primarily in the orientations of the styryl and the N -phenylcarboxamido groups. In the crystal, intermolecular N—H...N, C—H...O and C—H...S hydrogen-bonding contacts as well a C—H...π(ring) interactions lead to the formation of a layer structure parallel to (010). Hirshfeld surface analysis revealed that H...H interactions represent the main contributions to the crystal packing.