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

Nus, Meritxell; Sage, Andrew P; Lu, Yuning; Masters, Leanne; Lam, Brian Y H; Newland, Stephen; Weller, Sandra; Tsiantoulas, Dimitrios et al. · Nat Med · 2017

basic_science · Level V

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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 (T<sub>FH</sub>) 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-T<sub>FH</sub> cells, leading to PDL1-mediated suppression of T<sub>FH</sub> cell motility, alteration of T<sub>FH</sub> cell differentiation, reduced T<sub>FH</sub> abundance and suppression of the proatherogenic T<sub>FH</sub> response. Our findings reveal a previously unsuspected role for MZB cells in controlling the T<sub>FH</sub>-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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