Genetic deletion of IL-10 in DLBCL cells unexpectedly accelerates DLBCL progression. (A) Overall survival curves (and log-rank test statistic) of pBIC (IL-10 proficient), pBICΔ10 (IL-10 deficient), and pBICΔ10F/+ (IL-10 haplosufficient) mice. Time in the x-axis is represented as the time from the moment of birth in days. (B) Spleen length of pBIC and pBICΔ10 at early (115 days) or advanced (moribund mice) stages compared with control YC mice (t test). Representative images illustrate splenomegaly at advanced stages of disease compared with age-matched control YC mice. (C) Expansion of splenic lymphoma cells (CD19+ GFP+) at different stages of the disease when compared with normal GC B cells (CD19+ YFP+) from splenocytes of SRBC-immunized control YC mice (t test). (D) Representative fluorescence-activated cell sorter (FACS) profiles and cellular sizes as measured by FSC-A parameter of large lymphoma cells (CD19+ GFP+) or control GC B cells (CD19+ YFP+; ANOVA). (E) Representative FACS profiles and comparative levels of plasma cell marker CD138 within lymphoma cells (CD19+ GFP+) or control terminally differentiated PCs (YFP+ CD138+; ANOVA). (F) IHC staining of GFP/YFP (green) and hematoxylin (Hem) in control YC and lymphoma pBIC and pBICΔ10 mice (scale bar in μm). (G) Heat map showing z scores of ABC- and GCB-related genes and RNA-seq–based COO classifier revealing an ABC-DLBCL subtype in both pBIC/pBICΔ10 murine lymphomas, compared with normal GC B cells from control YC mice. (H) Heat map of Ig-related transcripts shows oligoclonality in both pBIC and pBICΔ10 models compared with normal GC B cells from control YC mice. ∗P < .05; ∗∗∗P < .001; d, days; FSC-A, forward scatter area; IHC, immunohistochemistry; MS, median survival; ns, nonsignificant; PCs, plasma cells; SRBC, sheep red blood cells.
