Ikaros prevents autoimmunity by controlling anergy and Toll-like receptor signaling in B cells
The establishment of a diverse B cell antigen receptor (BCR) repertoire by V(D)J recombination also generates autoreactive B cells. Anergy is one tolerance mechanism; it renders autoreactive B cells insensitive to stimulation by self-antigen, whereas Toll-like receptor (TLR) signaling can reactivate...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Research
2019
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| _version_ | 1826300548543938560 |
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| author | Schwickert, T Tagoh, H Schindler, K Fischer, M Jaritz, M Busslinger, M |
| author_facet | Schwickert, T Tagoh, H Schindler, K Fischer, M Jaritz, M Busslinger, M |
| author_sort | Schwickert, T |
| collection | OXFORD |
| description | The establishment of a diverse B cell antigen receptor (BCR) repertoire by V(D)J recombination also generates autoreactive B cells. Anergy is one tolerance mechanism; it renders autoreactive B cells insensitive to stimulation by self-antigen, whereas Toll-like receptor (TLR) signaling can reactivate anergic B cells. Here, we describe a critical role of the transcription factor Ikaros in controlling BCR anergy and TLR signaling. Mice with specific deletion of Ikaros in mature B cells developed systemic autoimmunity. Ikaros regulated many anergy-associated genes, including Zfp318, which is implicated in the attenuation of BCR responsiveness by promoting immunoglobulin D expression in anergic B cells. TLR signaling was hyperactive in Ikaros-deficient B cells, which failed to upregulate feedback inhibitors of the MyD88-nuclear factor κB signaling pathway. Systemic inflammation was lost on expression of a non-self-reactive BCR or loss of MyD88 in Ikaros-deficient B cells. Thus, Ikaros acts as a guardian preventing autoimmunity by promoting BCR anergy and restraining TLR signaling. |
| first_indexed | 2024-03-07T05:18:51Z |
| format | Journal article |
| id | oxford-uuid:de2c0918-4f9f-4075-81f8-b2ce8b5d70b2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:18:51Z |
| publishDate | 2019 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:de2c0918-4f9f-4075-81f8-b2ce8b5d70b22022-03-27T09:30:22ZIkaros prevents autoimmunity by controlling anergy and Toll-like receptor signaling in B cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:de2c0918-4f9f-4075-81f8-b2ce8b5d70b2EnglishSymplectic Elements at OxfordNature Research2019Schwickert, TTagoh, HSchindler, KFischer, MJaritz, MBusslinger, MThe establishment of a diverse B cell antigen receptor (BCR) repertoire by V(D)J recombination also generates autoreactive B cells. Anergy is one tolerance mechanism; it renders autoreactive B cells insensitive to stimulation by self-antigen, whereas Toll-like receptor (TLR) signaling can reactivate anergic B cells. Here, we describe a critical role of the transcription factor Ikaros in controlling BCR anergy and TLR signaling. Mice with specific deletion of Ikaros in mature B cells developed systemic autoimmunity. Ikaros regulated many anergy-associated genes, including Zfp318, which is implicated in the attenuation of BCR responsiveness by promoting immunoglobulin D expression in anergic B cells. TLR signaling was hyperactive in Ikaros-deficient B cells, which failed to upregulate feedback inhibitors of the MyD88-nuclear factor κB signaling pathway. Systemic inflammation was lost on expression of a non-self-reactive BCR or loss of MyD88 in Ikaros-deficient B cells. Thus, Ikaros acts as a guardian preventing autoimmunity by promoting BCR anergy and restraining TLR signaling. |
| spellingShingle | Schwickert, T Tagoh, H Schindler, K Fischer, M Jaritz, M Busslinger, M Ikaros prevents autoimmunity by controlling anergy and Toll-like receptor signaling in B cells |
| title | Ikaros prevents autoimmunity by controlling anergy and Toll-like receptor signaling in B cells |
| title_full | Ikaros prevents autoimmunity by controlling anergy and Toll-like receptor signaling in B cells |
| title_fullStr | Ikaros prevents autoimmunity by controlling anergy and Toll-like receptor signaling in B cells |
| title_full_unstemmed | Ikaros prevents autoimmunity by controlling anergy and Toll-like receptor signaling in B cells |
| title_short | Ikaros prevents autoimmunity by controlling anergy and Toll-like receptor signaling in B cells |
| title_sort | ikaros prevents autoimmunity by controlling anergy and toll like receptor signaling in b cells |
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