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

Akatsu C, Alborzian Deh Sheikh A, Matsubara N, Takematsu H, Schweizer A, Abdu-Allah HH, Tedder TF, Nitschke L, Ishida H, Tsubata T (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Science Signaling American Association for the Advancement of Science

Book Volume: 15

Pages Range: eabf9570-

Journal Issue: 723

DOI: 10.1126/scisignal.abf9570

Abstract

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-BCRhiCd45-/- 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.

Authors with CRIS profile

Astrid Schweizer Lars Nitschke Professur für Genetik

Involved external institutions

Tokyo Medical and Dental University (TMDU) / 東京医科歯科大学 JP Japan (JP) Fujita Health University JP Japan (JP) Gifu University / 岐阜大学 JP Japan (JP) Duke University Medical Center US United States (USA) (US)

How to cite

APA:

Akatsu, C., Alborzian Deh Sheikh, A., Matsubara, N., Takematsu, H., Schweizer, A., Abdu-Allah, H.H.,... Tsubata, T. (2022). The inhibitory coreceptor CD22 restores B cell signaling by developmentally regulating Cd45-/- immunodeficient B cells. Science Signaling, 15(723), eabf9570-. https://doi.org/10.1126/scisignal.abf9570

MLA:

Akatsu, Chizuru, et al. "The inhibitory coreceptor CD22 restores B cell signaling by developmentally regulating Cd45-/- immunodeficient B cells." Science Signaling 15.723 (2022): eabf9570-.

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