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Nat Med. 2017 May;23(5):601-610. doi: 10.1038/nm.4315. Epub 2017 Apr 17.

Marginal zone B cells control the response of follicular helper T cells to a high-cholesterol diet.

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Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK.
Metabolic Research Laboratories, University of Cambridge and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
Institut Necker-Enfants Malades, INSERM U1151, CNRS UMR 8253, Sorbonne, Paris Cité, Université Paris Descartes, Paris, France.
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria.
Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany.
Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University, Tübingen, Germany.
Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
Intercellular Signalling in Cardiovascular Development &Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Madrid, Spain.
INSERM, Unit 970, Paris Cardiovascular Research Center, Paris, France.


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.

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