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Types of tolerance seen in autoreactive phosphocholine-specific B cells are dependent on the idiotype of the receptors expressed

Cellular & Molecular Immunology volume 10, pages 311–316 (2013)Cite this article

Abstract

Phosphocholine (PC) is the immunodominant epitope found on the surface of a number of microorganisms, including Streptococcus pneumoniae (SPn), and is thought to play a vital role in the pathogenesis of SPn. B cells expressing M167Hκ24L immunoglobulin receptors specific for PC have been shown to be autoreactive in that they undergo clonal deletion in both X-linked immune-deficient and Rag−/− mice. We have now shown that B cells expressing M603Hκ8L PC-specific receptors also delete in Rag−/− mice, whereas those expressing T15Hκ22L transgenes do not delete. However, T15Hκ22L B cells are lost in normal heterozygous transgenic mice because they cannot compete with normal B cells. These data indicate that M167Hκ24L and M603Hκ8L PC-specific B cells are recognizing an autoantigen expressed on membranes which causes them to downregulate their receptors and clonally delete, while T15Hκ22L B cells are tolerized by a soluble form of PC-antigen which results in their being trapped in the spleen. Thus, the types of tolerance seen in autoreactive PC-specific B cells are dependent on the idiotype of the receptors expressed.

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Acknowledgements

We are grateful to Dr Klaus Rajewsky for providing T15i KI mice and mu KO mice, to Dr Ursula Storb for M167H chain mice and M167Hκ24L mice, and to J. Latham Claflin for M603 H and Kappa 8 L transgenic mice. We thank Randy Fisher, Anna Lustig and Dr Louis Razanka for technical assistance. This work was supported by the Gerontology Research Institute, NIA, NIH.

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Author notes

  1. James J Kenny: JJK was retired from Gerontology Research Institute, NIH, Baltimore.

Authors and Affiliations

  1. Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI, USA

    Qing-Sheng Mi

  2. Department of Dermatology, Henry Ford Health System, Detroit, MI, USA

    Qing-Sheng Mi

  3. Department of Internal Medicine, Henry Ford Health System, Detroit, MI, USA

    Qing-Sheng Mi

  4. Laboratory of Immunology, Gerontology Research Institute, NIH, Baltimore, MD, USA

    James J Kenny

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  1. Qing-Sheng Mi
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Correspondence to Qing-Sheng Mi.

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Mi, QS., Kenny, J. Types of tolerance seen in autoreactive phosphocholine-specific B cells are dependent on the idiotype of the receptors expressed. Cell Mol Immunol 10, 311–316 (2013). https://doi.org/10.1038/cmi.2013.17

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