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CD22 attenuates calcium signaling by potentiating plasma membrane calcium-ATPase activity

Nature Immunology volume 5, pages 651–657 (2004)Cite this article

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Abstract

Binding of antigen to the B cell receptor induces a calcium response, which is required for proliferation and antibody production. CD22, a B cell surface protein, inhibits this signal through mechanisms that have been obscure. We report here that CD22 augments calcium efflux after B cell receptor crosslinking. Inhibition of plasma membrane calcium-ATPase (PMCA) attenuated these effects, as did disruption by homologous recombination of the gene encoding PMCA4a and PMCA4b. PMCA coimmunoprecipitated with CD22 in an activation-dependent way. CD22 cytoplasmic tyrosine residues were required for association with PMCA and enhancement of calcium efflux. Moreover, CD22 regulation of efflux and the calcium response required the tyrosine phosphatase SHP-1. Thus, SHP-1 and PMCA provide a mechanism by which CD22, a tissue-specific negative regulator, can affect calcium responses.

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Figure 1: Negative regulation of Ca2+ signaling by CD22 is reversed by blocking of PMCA function.
Figure 2: CD22 enhances Ca2+ extrusion by the PMCA.
Figure 3: PMCA interaction with CD22 requires BCR stimulation.
Figure 4: Tyrosine phosphorylation of CD22 is required for the interaction between CD22 and PMCA.
Figure 5: SHP-1 is necessary for negative regulation of Ca2+ efflux by CD22.
Figure 6: Both CD22 and PMCA4 contribute to Ca2+ efflux from primary B cells.

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  • 16 May 2004

    appended aop PDF with erratum PDF (will be corrected for print issue), and placed footnote in XML at all occurrences of Figure 5

Notes

  1. *Note: In the version of this article originally published online, the key for Figure 5c and d was labeled incorrectly. The correct labels are "SHIPKO empty" and "SHIPKO CD22+." This error has been corrected for the HTML and print versions of this article.

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Acknowledgements

We thank R. Berland, K. Dunlap, E. Herrera, L. Jin, T. Imanishi-Kari and N. Rosenberg for discussions; E.A. Clark, D.L. Gill, M. Kurosaki and T. Kurosaki for reagents; and T. Trombley for help with some of the experiments. Supported by the National Institutes of Health (H.H.W., G.E.S. and B.G.N.).

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Author notes

  1. Paul A McLean

    Present address: Point Therapeutics, Boston, Massachusetts, 02111, USA

Authors and Affiliations

  1. Department of Pathology, Tufts University School of Medicine and Graduate Program in Genetics, Sackler School of Graduate Biomedical Sciences, Boston, 02111, Massachusetts, USA

    Jie Chen, Paul A McLean & Henry H Wortis

  2. Division of Hematology-Oncology, Department of Medicine, Cancer Biology Program, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, 02215, Massachusetts, USA

    Benjamin G Neel

  3. Department of Molecular Genetics, Biochemistry and Microbiology, The University of Cincinnati College of Medicine, Cincinnati, 45267, Ohio, USA

    Gbolahan Okunade & Gary E Shull

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Correspondence to Henry H Wortis.

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Chen, J., McLean, P., Neel, B. et al. CD22 attenuates calcium signaling by potentiating plasma membrane calcium-ATPase activity. Nat Immunol 5, 651–657 (2004). https://doi.org/10.1038/ni1072

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