Marginal zone B cells control the response of follicular helper T cells to a high-cholesterol diet
de la Pompa, JL
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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
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.
atherosclerosis, follicular B cells, marginal zone B cells
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.
British Heart Foundation (FS/15/57/31557)
EC FP7 MC IEF (351 - PCOFUND-GA-2013-608765)
External DOI: https://doi.org/10.1038/nm.4315
This record's URL: https://www.repository.cam.ac.uk/handle/1810/267872