Descatoire, Marc;
Fritzen, Remi;
Rotman, Samuel;
Kuntzelman, Genevieve;
Leber, Xavier Charles;
Droz-Georget, Stephanie;
Thrasher, Adrian J;
... Candotti, Fabio; + view all
(2022)
Critical role of WASp in germinal center tolerance through regulation of B cell apoptosis and diversification.
Cell Reports
, 38
(10)
, Article 110474. 10.1016/j.celrep.2022.110474.
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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.
| Type: | Article |
|---|---|
| Title: | Critical role of WASp in germinal center tolerance through regulation of B cell apoptosis and diversification |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2022.110474 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2022.110474 |
| Language: | English |
| Additional information: | © 2022 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10145589 |
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