Galectin-9 regulates the threshold of B cell activation and autoimmunity
Despite the mechanisms of central and peripheral tolerance, the mature B cell compartment contains cells reactive for self-antigen. How these cells are poised not to respond and the mechanisms that restrain B cell responses to low-affinity endogenous antigens are not fully understood. Here, we demon...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-08-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/64557 |
| _version_ | 1811180637656186880 |
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| author | Logan K Smith Kareem Fawaz Bebhinn Treanor |
| author_facet | Logan K Smith Kareem Fawaz Bebhinn Treanor |
| author_sort | Logan K Smith |
| collection | DOAJ |
| description | Despite the mechanisms of central and peripheral tolerance, the mature B cell compartment contains cells reactive for self-antigen. How these cells are poised not to respond and the mechanisms that restrain B cell responses to low-affinity endogenous antigens are not fully understood. Here, we demonstrate a critical role for the glycan-binding protein galectin-9 in setting the threshold of B cell activation and that loss of this regulatory network is sufficient to drive spontaneous autoimmunity. We further demonstrate a critical role for galectin-9 in restraining not only conventional B-2 B cells, but also innate-like B-1a cells. We show that galectin-9-deficient mice have an expanded population of B-1a cells and increased titers of B-1a-derived autoantibodies. Mechanistically, we demonstrate that galectin-9 regulates BCR and distinct TLR responses in B-1a cells, but not B-1b cells, by regulating the interaction between BCR and TLRs with the regulatory molecules CD5 and CD180, respectively. In the absence of galectin-9, B-1a cells are more readily activated and secrete increased titers of autoantibodies that facilitate autoantigen delivery to the spleen, driving autoimmune responses. |
| first_indexed | 2024-04-11T09:06:31Z |
| format | Article |
| id | doaj.art-c66710a569b94bf78c482cf16ed26ad6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:06:31Z |
| publishDate | 2021-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c66710a569b94bf78c482cf16ed26ad62022-12-22T04:32:37ZengeLife Sciences Publications LtdeLife2050-084X2021-08-011010.7554/eLife.64557Galectin-9 regulates the threshold of B cell activation and autoimmunityLogan K Smith0Kareem Fawaz1Bebhinn Treanor2https://orcid.org/0000-0002-8626-5944Department of Biological Sciences, University of Toronto Scarborough, Toronto, Canada; Department of Immunology, University of Toronto, Toronto, CanadaDepartment of Biological Sciences, University of Toronto Scarborough, Toronto, CanadaDepartment of Biological Sciences, University of Toronto Scarborough, Toronto, Canada; Department of Immunology, University of Toronto, Toronto, Canada; Department of Cell and Systems Biology, University of Toronto, Toronto, CanadaDespite the mechanisms of central and peripheral tolerance, the mature B cell compartment contains cells reactive for self-antigen. How these cells are poised not to respond and the mechanisms that restrain B cell responses to low-affinity endogenous antigens are not fully understood. Here, we demonstrate a critical role for the glycan-binding protein galectin-9 in setting the threshold of B cell activation and that loss of this regulatory network is sufficient to drive spontaneous autoimmunity. We further demonstrate a critical role for galectin-9 in restraining not only conventional B-2 B cells, but also innate-like B-1a cells. We show that galectin-9-deficient mice have an expanded population of B-1a cells and increased titers of B-1a-derived autoantibodies. Mechanistically, we demonstrate that galectin-9 regulates BCR and distinct TLR responses in B-1a cells, but not B-1b cells, by regulating the interaction between BCR and TLRs with the regulatory molecules CD5 and CD180, respectively. In the absence of galectin-9, B-1a cells are more readily activated and secrete increased titers of autoantibodies that facilitate autoantigen delivery to the spleen, driving autoimmune responses.https://elifesciences.org/articles/64557B cellsautoimmunitygalectin-9signalingB-1a cellsnanoclusters |
| spellingShingle | Logan K Smith Kareem Fawaz Bebhinn Treanor Galectin-9 regulates the threshold of B cell activation and autoimmunity eLife B cells autoimmunity galectin-9 signaling B-1a cells nanoclusters |
| title | Galectin-9 regulates the threshold of B cell activation and autoimmunity |
| title_full | Galectin-9 regulates the threshold of B cell activation and autoimmunity |
| title_fullStr | Galectin-9 regulates the threshold of B cell activation and autoimmunity |
| title_full_unstemmed | Galectin-9 regulates the threshold of B cell activation and autoimmunity |
| title_short | Galectin-9 regulates the threshold of B cell activation and autoimmunity |
| title_sort | galectin 9 regulates the threshold of b cell activation and autoimmunity |
| topic | B cells autoimmunity galectin-9 signaling B-1a cells nanoclusters |
| url | https://elifesciences.org/articles/64557 |
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