Figure 1
Figure 1. TCL1 reconstitutes the absent CD5+ B-cell population in PKCβ-deficient mice, but loss of PKCβ in TCL1 mice abrogates the CLL phenotype. (A) Flow cytometric analysis of the pretumor hyperplasia phenotype as present in the peritoneal cavity in indicated genotypes. Six-month-old mice were killed, and peritoneal cavity washes were analyzed for the content of CD5+CD19+ B cells (percentage of total cells in a lymphocyte gate are given in the graphs). Results from 6-month-old mice are shown as representative examples. Genotypes are abbreviated as follows: wild-type mice, WT; PKCβ-deficient mice, PKC−/−; TCL1 transgenic mice, TCL1; and the TCL1 transgenic mice with deleted PKCβ alleles, PKC−/− TCL1. (B) Graphs showing the percentage of CD5/CD19 double-positive cells (analyzed as shown in panel A) as individually represented values per mouse analyzed (means are represented by the horizontal lines), according to genotype (PKC+/− TCL1 denotes TCL1 transgenic mice with loss of a single PKCβ allele). Data from the peritoneal cavity (PC) and spleen are shown. Statistical comparisons were performed using unpaired t test (P values shown in Table S2). (C) Mice of indicated genotypes were followed until the development of signs of illness (TCL1, n = 45; PKC+/− TCL1, n = 20; PKC−/− TCL1, n = 21). Analysis of the organs was performed, and development of CLL was scored as an event. Kaplan-Meier plots of CLL-free survival are shown. Difference between groups proved statistically significant by log-rank test (TCL1 vs PKC+/− TCL1, P = .034; TCL1 vs PKC−/− TCL1, P < 0.001; PKC+/− TCL1 vs PKC−/− TCL1, P = .009). WT controls and PKC−/− mice did not develop CLL until more than 500 days. (D) Cells (2 × 105/well) were cultured in uncoated wells or wells coated with 5 μg/mL anti-IgM F(ab′)2 fragments for 24 hours. Cell viability of anti-IgM–treated B cells compared with untreated controls is shown for the indicated genotypes. Error bars represent SEM. Groups were compared by unpaired t test: WT versus PKC−/−, P = .036; TCL1 versus PKC−/− TCL1. P = .042.

TCL1 reconstitutes the absent CD5+ B-cell population in PKCβ-deficient mice, but loss of PKCβ in TCL1 mice abrogates the CLL phenotype. (A) Flow cytometric analysis of the pretumor hyperplasia phenotype as present in the peritoneal cavity in indicated genotypes. Six-month-old mice were killed, and peritoneal cavity washes were analyzed for the content of CD5+CD19+ B cells (percentage of total cells in a lymphocyte gate are given in the graphs). Results from 6-month-old mice are shown as representative examples. Genotypes are abbreviated as follows: wild-type mice, WT; PKCβ-deficient mice, PKC−/−; TCL1 transgenic mice, TCL1; and the TCL1 transgenic mice with deleted PKCβ alleles, PKC−/− TCL1. (B) Graphs showing the percentage of CD5/CD19 double-positive cells (analyzed as shown in panel A) as individually represented values per mouse analyzed (means are represented by the horizontal lines), according to genotype (PKC+/− TCL1 denotes TCL1 transgenic mice with loss of a single PKCβ allele). Data from the peritoneal cavity (PC) and spleen are shown. Statistical comparisons were performed using unpaired t test (P values shown in Table S2). (C) Mice of indicated genotypes were followed until the development of signs of illness (TCL1, n = 45; PKC+/− TCL1, n = 20; PKC−/− TCL1, n = 21). Analysis of the organs was performed, and development of CLL was scored as an event. Kaplan-Meier plots of CLL-free survival are shown. Difference between groups proved statistically significant by log-rank test (TCL1 vs PKC+/− TCL1, P = .034; TCL1 vs PKC−/− TCL1, P < 0.001; PKC+/− TCL1 vs PKC−/− TCL1, P = .009). WT controls and PKC−/− mice did not develop CLL until more than 500 days. (D) Cells (2 × 105/well) were cultured in uncoated wells or wells coated with 5 μg/mL anti-IgM F(ab′)2 fragments for 24 hours. Cell viability of anti-IgM–treated B cells compared with untreated controls is shown for the indicated genotypes. Error bars represent SEM. Groups were compared by unpaired t test: WT versus PKC−/−, P = .036; TCL1 versus PKC−/− TCL1. P = .042.

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