Marginal zone B cells control the response of follicular helper T cells to a high-cholesterol diet.
Meritxell NusAndrew P SageYuning LuLeanne MastersBrian Yee Hong LamStephen NewlandSandra WellerDimitrios TsiantoulasJuliette RaffortDamiënne MarcusAlison FiniganLauren KittNichola FiggReinhold SchirmbeckManfred KneillingGiles S H YeoChristoph J BinderJosé Luis de la PompaZiad MallatPublished in: Nature medicine (2017)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- endoplasmic reticulum stress
- physical activity
- dendritic cells
- oxidative stress
- type diabetes
- stem cells
- adipose tissue
- metabolic syndrome
- pseudomonas aeruginosa
- cell proliferation
- regulatory t cells
- transcription factor
- single cell
- cell therapy
- inflammatory response
- high fat diet induced
- skeletal muscle