Article ; Online: Critical role of WASp in germinal center tolerance through regulation of B cell apoptosis and diversification.
2022 Volume 38, Issue 10, Page(s) 110474
Abstract: A main feature of Wiskott-Aldrich syndrome (WAS) is increased susceptibility to autoimmunity. A key contribution of B cells to development of these complications has been demonstrated through studies of samples from affected individuals and mouse models ... ...
| Abstract | A main feature of Wiskott-Aldrich syndrome (WAS) is increased susceptibility to autoimmunity. A key contribution of B cells to development of these complications has been demonstrated through studies of samples from affected individuals and mouse models of the disease, but the role of the WAS protein (WASp) in controlling peripheral tolerance has not been specifically explored. Here we show that B cell responses remain T cell dependent in constitutive WASp-deficient mice, whereas selective WASp deletion in germinal center B cells (GCBs) is sufficient to induce broad development of self-reactive antibodies and kidney pathology, pointing to loss of germinal center tolerance as a primary cause leading to autoimmunity. Mechanistically, we show that WASp is upregulated in GCBs and regulates apoptosis and plasma cell differentiation in the germinal center and that the somatic hypermutation-derived diversification is the basis of autoantibody development. |
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| MeSH term(s) | Animals ; Apoptosis ; Autoantibodies ; Germinal Center/pathology ; Mice ; Mice, Knockout ; Wasps ; Wiskott-Aldrich Syndrome/pathology |
| Chemical Substances | Autoantibodies |
| Language | English |
| Publishing date | 2022-03-19 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2649101-1 |
| ISSN | 2211-1247 ; 2211-1247 |
| ISSN (online) | 2211-1247 |
| ISSN | 2211-1247 |
| DOI | 10.1016/j.celrep.2022.110474 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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