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  Defective Allelic Exclusion by IgD in the Absence of Autoantigen

Renna, V., Surova, E., Khadour, A., Datta, M., Amendt, T., Hobeika, E., et al. (2022). Defective Allelic Exclusion by IgD in the Absence of Autoantigen. The Journal of Immunology, 208, 293-302. doi:10.4049/jimmunol.2100726.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000D-1D84-E Version Permalink: https://hdl.handle.net/21.11116/0000-000D-1D85-D
Genre: Journal Article

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10.4049_jimmunol.2100726.pdf (Publisher version), 2MB
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https://hdl.handle.net/21.11116/0000-000D-1D86-C
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10.4049_jimmunol.2100726.pdf
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2022
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by The American Association of Immunologists, Inc.
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https://journals.aai.org/jimmunol/article/208/2/293/234721/Defective-Allelic-Exclusion-by-IgD-in-the-Absence (Publisher version)
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 Creators:
Renna, Valerio1, Author
Surova, Elena2, Author
Khadour, Ahmad1, Author
Datta, Moumita1, Author
Amendt, Timm1, Author
Hobeika, Elias1, Author
Jumaa, Hassan1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243648              

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 Abstract: A considerable proportion of peripheral B cells is autoreactive, and it is unclear how the activation of such potentially harmful cells is regulated. In this study, we show that the different activation thresholds or IgM and IgD BCRs adjust B cell activation to the diverse requirements during development. We rely on the autoreactive 3-83 model BCR to generate and analyze mice expressing exclusively autoreactive IgD BCRs on two different backgrounds that determine two stages of autoreactivity, depending on the presence or absence of the cognate Ag. By comparing these models with IgM-expressing control mice, we found that, compared with IgM, IgD has a higher activation threshold in vivo, as it requires autoantigen to enable normal B cell development, including allelic exclusion. Our data indicate that IgM provides the high sensitivity required during early developmental stages to trigger editing of any autoreactive specificities, including those enabling weak interaction with autoantigen. In contrast, IgD has the unique ability to neglect weakly interacting autoantigens while retaining reactivity to higher-affinity Ag. This IgD function enables mature B cells to ignore autoantigens while remaining able to efficiently respond to foreign threats.

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Language(s): eng - English
 Dates: 2022-01-15
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.4049/jimmunol.2100726
 Degree: -

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Title: The Journal of Immunology
  Other : J. Immunol.
Source Genre: Journal
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Publ. Info: Baltimore, U.S.A. : Williams & Wilkins
Pages: - Volume / Issue: 208 Sequence Number: - Start / End Page: 293 - 302 Identifier: ISSN: 0022-1767
CoNE: https://pure.mpg.de/cone/journals/resource/954925414915_1