Marginal zone B cells control the response of follicular helper T cells to a high-cholesterol diet
Authors
Masters, L
Newland, Stephen
Weller, S
Tsiantoulas, Dimitrios
Raffort, J
Marcus, D
Finigan, A
Kitt, L
Figg, N
Schirmbeck, R
Kneilling, M
Binder, CJ
de la Pompa, JL
Publication Date
2017-05Journal Title
Nature Medicine
ISSN
1078-8956
Publisher
Springer Nature
Volume
23
Issue
5
Pages
601-610
Language
eng
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Nus Chimeno, M., Sage, A., Lu, Y., Masters, L., Lam, B., Newland, S., Weller, S., et al. (2017). Marginal zone B cells control the response of follicular helper T cells to a high-cholesterol diet. Nature Medicine, 23 (5), 601-610. https://doi.org/10.1038/nm.4315
Abstract
Splenic marginal zone B (MZB) cells, positioned at the interface between circulating blood and lymphoid tissue, detect and respond to blood-borne antigens. Here we show that MZB cells in mice activate a homeostatic program in response to a high-cholesterol diet (HCD) and regulate both the differentiation and accumulation of T follicular helper (TFH) cells. Feeding mice an HCD resulted in upregulated MZB cell surface expression of the immunoregulatory ligand PDL1 in an ATF3-dependent manner and increased the interaction between MZB cells and pre-TFH cells, leading to PDL1-mediated suppression of TFH cell motility, alteration of TFH cell differentiation, reduced TFH abundance and suppression of the proatherogenic TFH response. Our findings reveal a previously unsuspected role for MZB cells in controlling the TFH–germinal center response to a cholesterol-rich diet and uncover a PDL1-dependent mechanism through which MZB cells use their innate immune properties to limit an exaggerated adaptive immune response.
Keywords
atherosclerosis, follicular B cells, marginal zone B cells
Sponsorship
This work was supported by BHF grant no. PG/15/76/31756, BHF grant no. PG/13/73/30466, ERC grant no. 2891164 and EC FP7 VIA grant no. HEALTH-F4- 2013-603131 to Z.M. and by SAF2013-45543-R from the Spanish Ministry of Economy and Competitiveness (MINECO) to J.L.d.l.P. M.N. was first supported by a Sara Borrell grant (CD09/00452) from the Instituto Nacional de Salud Carlos III (Spain) and then by a 2-year BHF Project Grant. M.N. has also received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 608765. The Wellcome Trust supported the Cambridge Mouse Biochemistry Laboratory.
Funder references
British Heart Foundation (FS/15/57/31557)
European Commission (608765)
British Heart Foundation (None)
British Heart Foundation (PG/15/76/31756)
Identifiers
External DOI: https://doi.org/10.1038/nm.4315
This record's URL: https://www.repository.cam.ac.uk/handle/1810/267872
Rights
Licence:
http://www.rioxx.net/licenses/all-rights-reserved
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.