Figure 5.
BAFF controls the homeostatic survival response to venetoclax treatment in B cells. (A) Schematic representation of hematopoietic chimeras reconstituted with a mixture of CD45.2+, Bak–/–BaxΔcd23, and CD45.1+ wt BM progenitors, followed by venetoclax treatment. (B) Total numbers of splenic B cells of Bak–/–BaxΔcd23 or wt origin recovered from vehicle- and venetoclax-treated chimeras. (C) Histograms of BCL-2, MCL-1, and BCL-XL staining gated on splenic B cells of wt or Bak–/–BaxΔcd23 origin recovered from the chimeric recipient mice treated with vehicle or venetoclax. (D) Geometric mean of BCL-2, MCL-1, and BCL-XL protein expression levels in splenic B cells of Bak–/–BaxΔcd23 or wt origin recovered from the vehicle- or venetoclax-treated chimeric recipient mice. (E) Serum BAFF from wt and Bak–/–BaxΔcd23 mice after 7-day treatment of venetoclax. Data are from 2 experiments with n = 2 to 3. (F) Schematic representation of the experimental design. Purified CD45.2+ C57BL/6 B cells from Bak–/–BaxΔcd23 or Tnfrsf13c–/–Bak–/–BaxΔcd23 mice were transferred into venetoclax-treated CD45.1+ C57BL/6 wt recipient mice, which were then maintained on daily venetoclax treatment before analysis. (G) Histograms of BCL-2, MCL-1, and BCL-XL protein expression in donor CD45.2+ B cells from unmanipulated control mice with the same genotype or from venetoclax treated recipients. (H) Geometric mean of BCL-2, MCL-1, and BCL-XL protein expression in Bak–/–BaxΔcd23 and Tnfrsf13c–/–Bak–/–BaxΔcd23 B cells from control (untreated) recipient mice or from venetoclax-treated recipient mice as indicated in (F), measured by flow cytometry. (I) Fold change in BCL-2, MCL-1, and BCL-XL protein levels in Bak–/–BaxΔcd23 and Tnfrsf13c–/–Bak–/–BaxΔcd23 B cells in venetoclax-treated mice. The data are expressed relative to the MFI in B cells recovered from unmanipulated control mice of the same genotype. Data from panels B-H are representative of 3 independent experiments with n = 3 to 6 mice per group. For all bar graphs, the mean ± SEM are shown and each symbol represents an individual mouse; Student 2-tailed t test was used. ∗P < .05; ∗∗P < .01; ∗∗∗P < .005; ∗∗∗∗P < .001. ELISA, enzyme-linked immunosorbent assay; MFI, mean fluorescence intensity.

BAFF controls the homeostatic survival response to venetoclax treatment in B cells. (A) Schematic representation of hematopoietic chimeras reconstituted with a mixture of CD45.2+, Bak–/–BaxΔcd23, and CD45.1+ wt BM progenitors, followed by venetoclax treatment. (B) Total numbers of splenic B cells of Bak–/–BaxΔcd23 or wt origin recovered from vehicle- and venetoclax-treated chimeras. (C) Histograms of BCL-2, MCL-1, and BCL-XL staining gated on splenic B cells of wt or Bak–/–BaxΔcd23 origin recovered from the chimeric recipient mice treated with vehicle or venetoclax. (D) Geometric mean of BCL-2, MCL-1, and BCL-XL protein expression levels in splenic B cells of Bak–/–BaxΔcd23 or wt origin recovered from the vehicle- or venetoclax-treated chimeric recipient mice. (E) Serum BAFF from wt and Bak–/–BaxΔcd23 mice after 7-day treatment of venetoclax. Data are from 2 experiments with n = 2 to 3. (F) Schematic representation of the experimental design. Purified CD45.2+ C57BL/6 B cells from Bak–/–BaxΔcd23 or Tnfrsf13c–/–Bak–/–BaxΔcd23 mice were transferred into venetoclax-treated CD45.1+ C57BL/6 wt recipient mice, which were then maintained on daily venetoclax treatment before analysis. (G) Histograms of BCL-2, MCL-1, and BCL-XL protein expression in donor CD45.2+ B cells from unmanipulated control mice with the same genotype or from venetoclax treated recipients. (H) Geometric mean of BCL-2, MCL-1, and BCL-XL protein expression in Bak–/–BaxΔcd23 and Tnfrsf13c–/–Bak–/–BaxΔcd23 B cells from control (untreated) recipient mice or from venetoclax-treated recipient mice as indicated in (F), measured by flow cytometry. (I) Fold change in BCL-2, MCL-1, and BCL-XL protein levels in Bak–/–BaxΔcd23 and Tnfrsf13c–/–Bak–/–BaxΔcd23 B cells in venetoclax-treated mice. The data are expressed relative to the MFI in B cells recovered from unmanipulated control mice of the same genotype. Data from panels B-H are representative of 3 independent experiments with n = 3 to 6 mice per group. For all bar graphs, the mean ± SEM are shown and each symbol represents an individual mouse; Student 2-tailed t test was used. ∗P < .05; ∗∗P < .01; ∗∗∗P < .005; ∗∗∗∗P < .001. ELISA, enzyme-linked immunosorbent assay; MFI, mean fluorescence intensity.

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