Nr4a1 (nerve growth factor IB) deletion in marginal zone B (MZB) cells increases atherosclerosis development.
Ldlr−/−; Cd79aCre/+; Rbpjkflox/flox were partially irradiated (Materials and Methods in the Data Supplement) and transplanted with WT (wild type; for reconstitution with WT MZB cells) or Nr4a1−/− (for reconstitution with Nr4a1−/− MZB cells) BM and fed a high-fat/high-cholesterol diet for 8 wk (A–H). A, Representative Masson trichrome staining and quantification of atherosclerotic plaques in aortic roots (each symbol represents one mouse, and horizontal bars are group mean±SEM with n=16–18 in each group). Original magnification, ×10. Scale bars=500 μm. B–D, Total plasma cholesterol, HDL (high-density lipoprotein) cholesterol, and triglycerides levels. E and F, Total numbers of T follicular helper (Tfh) and germinal center (GC) B cells. Cd274 (Pdl1 [programmed death ligand-1] gene) expression, quantified by qRT-PCR (n=5 in each group) in sorted MZB cells (G) and PDL1 protein expression, quantified by flow cytometry in splenic MZB cells (H; n=16–18 in each group). For A–G, 2-tailed unpaired Student t test or 2-way ANOVA followed by Bonferroni post hoc analysis, *P<0.05 and **P<0.01. MFI indicates mean fluorescence intensity; and PDL1, programmed cell death ligand-1.