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CD22 regulates B lymphocyte function in vivo through both ligand-dependent and ligand-independent mechanisms

Nature Immunology volume 5, pages 1078–1087 (2004)Cite this article

Abstract

The interaction of CD22 with α2,6-linked sialic acid ligands has been widely proposed to regulate B lymphocyte function and migration. Here, we generated gene-targeted mice that express mutant CD22 molecules that do not interact with these ligands. CD22 ligand binding regulated the expression of cell surface CD22, immunoglobulin M and major histocompatibility complex class II on mature B cells, maintenance of the marginal zone B cell population, optimal B cell antigen receptor–induced proliferation, and B cell turnover rates. However, CD22 negative regulation of calcium mobilization after B cell antigen receptor ligation, CD22 phosphorylation, recruitment of SHP-1 to CD22 and B cell migration did not require CD22 ligand engagement. These observations resolve longstanding questions regarding the physiological importance of CD22 ligand binding in the regulation of B cell function in vivo.

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Figure 1: Generation of CD22Δ1-2 and CD22AA mice.
Figure 2: B cell phenotypes in CD22Δ1-2 and CD22AA mice.
Figure 3: Calcium mobilization, CD22 tyrosine phosphorylation and CD22 recruitment of SHP-1 are normal in CD22Δ1-2 and CD22AA B cells.
Figure 4: Altered proliferative responses of B cells from CD22Δ1-2 and CD22AA mice.
Figure 5: Altered B cell turnover in CD22Δ1-2 and CD22AA mice.
Figure 6: CD22 ligand binding does not promote B cell migration.

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Acknowledgements

We thank A. Jackson, A. Meade and I. Dzhagalov for assistance with real-time PCR assays. Supported by the National Institutes of Health (CA96547, CA81776 and AI56363) and a Biomedical Science Grant from the Arthritis Foundation (to T.F.T.).

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Author notes

  1. Minoru Hasegawa

    Present address: Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa, Japan, 920-8641

  2. Manabu Fujimoto

    Present address: Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-8655

  3. Jonathan C Poe and Yoko Fujimoto: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Jonathan C Poe, Yoko Fujimoto, Minoru Hasegawa, Karen M Haas, Ann S Miller, Isaac G Sanford, Cheryl B Bock, Manabu Fujimoto & Thomas F Tedder

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Correspondence to Thomas F Tedder.

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Competing interests

T. Tedder has a personal financial interest in Cellective Therapeutics, which is developing CD22-directed therapies for the treatment of oncology and autoimmunity.

Supplementary information

Supplementary Fig. 1

Cd22 gene targeting in CD22AA mice assessed by Southern hybridization of Kpn I-Xho I digested genomic DNA using DNA probe A, specific for a region of the Cd22 gene outside of the targeting vector. (PDF 149 kb)

Supplementary Methods (PDF 5 kb)

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Poe, J., Fujimoto, Y., Hasegawa, M. et al. CD22 regulates B lymphocyte function in vivo through both ligand-dependent and ligand-independent mechanisms. Nat Immunol 5, 1078–1087 (2004). https://doi.org/10.1038/ni1121

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