Btg1 deletion is a driver of lymphomagenesis. (A-B) Flow cytometry quantification of splenic GC B cells (CD19+, B220+, CD95+, GL7+) 9 days after SRBC immunization in Btg1−/− or Btg1WT mice. Top panel: percentage of GC B cells in the spleen of Btg1−/− or Btg1WT mice with or without SRBC immunization (n = 4 in control group, n = 5 in SRBC-treated group). Bottom panel: example of flow cytometry histograms. (B) Flow cytometry quantification of splenic NP-CGG–specific GC B cells (CD19+, B220+, CD95+, GL7+, IgG1+, IgM−, IgD−, NP+) 9 days after NP-CGG (7) immunization in Btg1−/− or Btg1WT mice. Top panel: percentage of NP+ cells in the spleen of Btg1−/− or Btg1WT mice with or without NP-CGG (7) immunization (n = 5 in untreated groups, n = 4 in Btg1WT-treated group, n = 5 in Btg1−/−-treated group). Bottom panel: example of flow cytometry histograms. (C) Representative histological analysis of the spleens (top) and quantification (bottom) of SRBC-immunized Btg1−/− or Btg1WT mice after staining with peanut agglutinin or Ki67 antibody. (D) Kaplan-Meier survival probability of irradiated mice engrafted with VavP-Bcl2-Btg1−/−(blue, n = 15) and VavP-Bcl2-Btg1WT (red, n = 15; P = .0089). (E) Absolute quantification of the number of B cells in spleen (left) and liver (right) upon sacrifice (Btg1WT, n = 6; Btg1−/−, n = 12). (F) B220 staining of representative spleen sections from VavP-Bcl2-Btg1−/− and VavP-Bcl2-Btg1WT recipients. (G) Quantification of the clonal composition of spleens from VavP-Bcl2-Btg1WT and VavP-Bcl2-Btg1−/− recipients (n = 4). The numbers above the histograms represent the percentage of reads corresponding to the largest clone over the 100 most represented. Right panel: comparison of the mean proportion of the major clone between VavP-BCL2-Btg1WT and VavP-BCL2-BTG1−/− recipients (P = .0286). Values represent mean ± SEM; ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001; using the Mann-Whitney test in panels A-C,E-G or log-rank (Mantel-Cox) test in panel D. ns, not significant; SEM, standard error of the mean; SRBC, sheep red blood cells.
Figure 1.

Btg1 deletion is a driver of lymphomagenesis. (A-B) Flow cytometry quantification of splenic GC B cells (CD19+, B220+, CD95+, GL7+) 9 days after SRBC immunization in Btg1−/− or Btg1WT mice. Top panel: percentage of GC B cells in the spleen of Btg1−/− or Btg1WT mice with or without SRBC immunization (n = 4 in control group, n = 5 in SRBC-treated group). Bottom panel: example of flow cytometry histograms. (B) Flow cytometry quantification of splenic NP-CGG–specific GC B cells (CD19+, B220+, CD95+, GL7+, IgG1+, IgM, IgD, NP+) 9 days after NP-CGG (7) immunization in Btg1−/− or Btg1WT mice. Top panel: percentage of NP+ cells in the spleen of Btg1−/− or Btg1WT mice with or without NP-CGG (7) immunization (n = 5 in untreated groups, n = 4 in Btg1WT-treated group, n = 5 in Btg1−/−-treated group). Bottom panel: example of flow cytometry histograms. (C) Representative histological analysis of the spleens (top) and quantification (bottom) of SRBC-immunized Btg1−/− or Btg1WT mice after staining with peanut agglutinin or Ki67 antibody. (D) Kaplan-Meier survival probability of irradiated mice engrafted with VavP-Bcl2-Btg1−/−(blue, n = 15) and VavP-Bcl2-Btg1WT (red, n = 15; P = .0089). (E) Absolute quantification of the number of B cells in spleen (left) and liver (right) upon sacrifice (Btg1WT, n = 6; Btg1−/−, n = 12). (F) B220 staining of representative spleen sections from VavP-Bcl2-Btg1−/− and VavP-Bcl2-Btg1WT recipients. (G) Quantification of the clonal composition of spleens from VavP-Bcl2-Btg1WT and VavP-Bcl2-Btg1−/− recipients (n = 4). The numbers above the histograms represent the percentage of reads corresponding to the largest clone over the 100 most represented. Right panel: comparison of the mean proportion of the major clone between VavP-BCL2-Btg1WT and VavP-BCL2-BTG1−/− recipients (P = .0286). Values represent mean ± SEM; ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001; using the Mann-Whitney test in panels A-C,E-G or log-rank (Mantel-Cox) test in panel D. ns, not significant; SEM, standard error of the mean; SRBC, sheep red blood cells.

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