The inhibitory coreceptor CD22 restores B cell signaling by developmentally regulating Cd45−/− immunodeficient B cells

Chizuru Akatsu, Amin Alborzian Deh Sheikh, Naoko Matsubara, Hiromu Takematsu, Astrid Schweizer, Hajjaj H.M. Abdu-Allah, Thomas F. Tedder, Lars Nitschke, Hideharu Ishida, Takeshi Tsubata

研究成果: Article査読

抄録

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-BCRhi 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.

本文言語English
論文番号eabf9570
ジャーナルScience Signaling
15
723
DOI
出版ステータスPublished - 01-03-2022

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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