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Ablation of CD22 in ligand-deficient mice restores B cell receptor signaling

Nature Immunology volume 7, pages 199–206 (2006)Cite this article

Abstract

CD22 is a negative regulator of B cell signaling, an activity modulated by its interaction with glycan ligands containing α2-6-linked sialic acids. B cells deficient in the enzyme (ST6Gal I) that forms the CD22 ligand show suppressed BCR signaling. Here we report that mice deficient in both CD22 and its ligand (Cd22−/−St6gal1−/− mice) showed restored B cell receptor (BCR) signaling, suggesting that the suppressed signaling of St6gal1−/− cells is mediated through CD22. Coincident with suppressed BCR signaling, B cells lacking ST6Gal I showed a net redistribution of the BCR to clathrin-rich microdomains containing most of the CD22, resulting in a twofold increase in the localization of CD22 together with the BCR. These studies suggest an important function for the CD22-ligand interaction in regulating BCR signaling and microdomain localization.

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Figure 1: Ablation of CD22 and its ligands in double-knockout mice.
Figure 2: Restored BCR-mediated signaling of double-knockout B cells.
Figure 3: Increased localization of CD22 and surface IgM in the absence of CD22 ligands.
Figure 4: Increased localization of CD22 together with surface IgM in GM1- and clathrin-rich membrane microdomains.
Figure 5: Microdomain localization of surface IgM in double-knockout cells is restored, whereas ST6Gal I–deficient B cells have altered surface IgM microdomain localization.

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Acknowledgements

We thank J. Marth and L. Nitschke for ST6Gal I–deficient and CD22-deficient mice, respectively; H. Li and M. Iufer for technical assistance and A. Tran-Crie for assistance in manuscript preparation. Supported by the National Institutes of Health (AI050143 to J.C.P. and GM25042 to B.E.C.) and the Wenner-Gren Foundation (P.B.)

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Author notes

  1. Per Bengtson

    Present address: Department of Clinical Science, Division of Oncology, Lund University, 22185, Lund, Sweden

  2. Brian E Collins and Brian A Smith: These authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Molecular Biology and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, 92037, California, USA

    Brian E Collins, Per Bengtson & James C Paulson

  2. Sidney Kimmel Cancer Center, La Jolla, 92037, California, USA

    Brian A Smith

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Correspondence to James C Paulson.

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Supplementary information

Supplementary Fig. 1

Restored phosphorylation of cytoplasmic proteins in B cells from double-knockout mice. (PDF 521 kb)

Supplementary Fig. 2

Similar CD22 and IgM co-clustering following BCR crosslinking on B cells from WT or ST6Gal I null mice. (PDF 89 kb)

Supplementary Methods (PDF 52 kb)

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Collins, B., Smith, B., Bengtson, P. et al. Ablation of CD22 in ligand-deficient mice restores B cell receptor signaling. Nat Immunol 7, 199–206 (2006). https://doi.org/10.1038/ni1283

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