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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Akatsu, C; Alborzian Deh Sheikh, A; Matsubara, N; Takematsu, H; Schweizer, A; Abdu-Allah, HHM; Tedder, TF; Nitschke, L; Ishida, H; Tsubata, T

Published Date

  • March 2022

Published In

Volume / Issue

  • 15 / 723

Start / End Page

  • eabf9570 -

PubMed ID

  • 35230871

Electronic International Standard Serial Number (EISSN)

  • 1937-9145

Digital Object Identifier (DOI)

  • 10.1126/scisignal.abf9570

Language

  • eng

Conference Location

  • United States