Figure 5. Alterations in circulating B cells precede ICI-colitis.
(A) Experimental scheme on ICI-colitis induction and tissue collection (n = 5 per group).
(B–D) Proportion of B and T cells in PB, mLNs, and colons out of CD45.2+ cells in healthy mice and colitis-susceptible mice prior to and following 2 doses of combo ICIs.
(E–G) Normalized heatmap of number of B cells (as % of live cells) expressing various molecules in mLNs, colons, and PB of colitis-susceptible mice prior to and after 2 or 3 doses of combo ICIs.
(H–K) Proportion of DCs and Mϕs in mLNs and colons out of CD45.2+ cells.
(L) Experimental scheme of ICI-colitis induction in mice pretreated with anti-CD19/anti-B220/anti-CD22 mAbs and tissue collection (n = 5 per group).
(M–O) Frequency of DC subsets as a fraction of live cells in colons and mLNs.
(P) Normalized heatmap of median fluorescent intensity (MFI) of marker expression by mLN DC subsets following combo ICIs with and without B cell blockade.
(Q and R) PCA biplot of markers expressed by T cells from colons and mLNs of mice following combo ICIs with and without B cell blockade with the nine most contributing loadings. Experiments were repeated three times with similar results.
Mean ± SEM; ANOVA tests with Tukey post hoc. ns: no significance, *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.