Fig. 4: TCF1 and LEF1 promote IL-10 production by B-1a cells and their control of CNS inflammation.
From: TCF1 and LEF1 promote B-1a cell homeostasis and regulatory function
a, UMAP showing clonal BCR usage in clusters of peritoneal B cells and expression of Tcf7, Cd5 and Ctla4. b, Gene module scores associated with gene signatures. c, PDL1 histograms and gMFI in the indicated cell subsets (n = 8). d,e, Flow cytometry plots and quantification of IL-10+ cells in TCF1high or TCF1low PC B1 cells (n = 6; d) and IL-10+ cells within PC B1 cells from TCF1WTLEF1WT (n = 11) and TCF1ΔLEF1Δ mice (n = 5; e). f, Expression of CD5, CD21, CD1d and B220 by CD19lowIL-10+ (blue), CD19highIL-10+ (red) and IL-10− (grey) cells with or without stimulation. g, TCF1 and LEF1 histograms (left) and quantification (right) in the cell subset shown in panel f (n = 3). h, Pseudocolour plots and quantification of IL-10+ splenic B cells from TCF1WTLEF1WT (n = 6) and TCF1ΔLEF1Δ (n = 4) mice. i,j, Correlation analysis between TCF1 or LEF1 expression and the percentage of IL-10+ cells (n = 6; i) or expression of CD5 and the percentage of IL-10+ in peritoneal B-1a cells from TCF1WTLEF1WT (n = 5) and TCF1ΔLEF1Δ (n = 5; j). k, Mean clinical scores of mice treated with either PBS (n = 5) or adoptively transferred with peritoneal B-1 cells from TCF1WTLEF1WT (n = 5) or TCF1ΔLEF1Δ (n = 5). l–n, Contour plots of GRM2A-positive cells within the indicated cell populations from the peritoneal cavity (l,m) and the spleen (n). o, Identification of GRM2A-positive B-1 cells in the EAE mouse brain; representative cells are from the area labelled ‘i’. Representative cells from the areas labelled ‘ii–iv’ are shown in Extended Data Fig. 7h. Each symbol represents an individual mouse, and the bars represent the median values (c–e,g,h). Data are presented as mean ± s.e.m. (k). Data are representative of n = 2 experiments (c–e,g–k) and n = 3 mice (l). Statistical analysis was performed using two-tailed Pearson correlation analysis (i,j), two-tailed Mann–Whitney t-test (h), one-way ANOVA with Tukey multiple-comparison test (c–e,g) and two-way ANOVA (k). The exact P values are shown.
