Newman, R;
Tolar, P;
(2021)
Chronic calcium signaling in IgE⁺ B cells limits plasma cell differentiation and survival.
Immunity
, 54
(12)
2756-2771.e10.
10.1016/j.immuni.2021.11.006.
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Abstract
In contrast to other antibody isotypes, B cells switched to IgE respond transiently and do not give rise to long-lived plasma cells (PCs) or memory B cells. To better understand IgE-BCR-mediated control of IgE responses, we developed whole-genome CRISPR screening that enabled comparison of IgE+ and IgG1+ B cell requirements for proliferation, survival, and differentiation into PCs. IgE+ PCs exhibited dependency on the PI3K-mTOR axis that increased protein amounts of the transcription factor IRF4. In contrast, loss of components of the calcium-calcineurin-NFAT pathway promoted IgE+ PC differentiation. Mice bearing a B cell-specific deletion of calcineurin B1 exhibited increased production of IgE+ PCs. Mechanistically, sustained elevation of intracellular calcium in IgE+ PCs downstream of the IgE-BCR promoted BCL2L11-dependent apoptosis. Thus, chronic calcium signaling downstream of the IgE-BCR controls the self-limiting character of IgE responses and may be relevant to the accumulation of IgE-producing cells in allergic disease.
| Type: | Article |
|---|---|
| Title: | Chronic calcium signaling in IgE⁺ B cells limits plasma cell differentiation and survival |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.immuni.2021.11.006 |
| Publisher version: | https://doi.org/10.1016/j.immuni.2021.11.006 |
| Language: | English |
| Additional information: | Copyright © 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | CRISPR-Cas9, IgE, B cells, BCR, plasma cells, calcium signaling, mTOR, apoptosis, mitochondria |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10140756 |
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