Figure 7.
Figure 7. DNA repair deficiency in preB cells and control of IL-7 expression in vivo. (A) Longitudinal 30-µm-thick femur section of lethally irradiated Il7GFP/+ Cxcl12dsRed/+ mice reconstituted with Rag1−/− VH147Igh Eμ-Bcl2 (top panels) or Dclrec1−/− VH147Igh Eμ-Bcl2 BM stained to detect GFP (green), CD19 (cyan), and cell nuclei (DAPI, not shown). Cxcl12-dsRed fluorescent protein (red) was directly visualized. Scale bar, 50 µm. Images are representative of three individual mice. (B) Quantification of Artemis-deficient (blue) and -sufficient (red) preB cells in contact with IL-7– and CXCL12-producing cells. Bars indicate mean; circles depict individual mice (n = 3). (C) CXCR4 expression in Artemis-deficient (blue) and -sufficient (red) preB cells in vivo. Numbers indicate geometric mean fluorescence intensity (GMFI) ± SD (n = 3). (D) Il7-GFP expression in nonhematopoietic Lepr+ BM cells of lethally irradiated Il7GFP/+ mice reconstituted with Rag1−/− VH147Igh Eμ-Bcl2 or Dclrec1−/− VH147Igh Eμ-Bcl2 BM cells. (E) Quantification of Il7-GFP expression from D. (F) Geometric mean fluorescence intensity of Il7-GFP expression in nonhematopoietic Lepr+ BM cells of Il7GFP/+ mice 2 wk after transfer of 105 BCR-ABL transduced preB cells. (G) Quantification of Il7-GFP expression from F. (H) Geometric mean fluorescence intensity of Cxcl12-dsRed expression in nonhematopoietic Lepr+ BM cells of Cxcl12dsred/+ Il7GFP/+ mice 2 wk after transfer of 105 BCR-ABL preB cells. (I) Quantification of Cxcl12-dsRed expression from H. Lines indicate mean; circles depict individual mice analyzed (n = 3). (J) Terminal deoxynucleotidyl transferase (Tdt) expression in nonleukemic proB cells isolated from mice described in H. (K) Quantification of terminal deoxynucleotidyl transferase expression from J. (L and M) Total CD19+ host B lymphocytes (L) and granulocytes (M) 2 wk after transfer of 105 BCR-ABL transduced preB cells. (E, G, and K–M) Lines indicate mean; circles depict individual mice analyzed (n = 3). (N) Model of damaged preB or preB-ALL cell/IL-7+ cell circuit. Data in all panels are representative of two to four independent experiments. *, P < 0.05; **, P < 0.01; ***, P < 0.001.

DNA repair deficiency in preB cells and control of IL-7 expression in vivo. (A) Longitudinal 30-µm-thick femur section of lethally irradiated Il7GFP/+ Cxcl12dsRed/+ mice reconstituted with Rag1−/− VH147Igh Eμ-Bcl2 (top panels) or Dclrec1−/− VH147Igh Eμ-Bcl2 BM stained to detect GFP (green), CD19 (cyan), and cell nuclei (DAPI, not shown). Cxcl12-dsRed fluorescent protein (red) was directly visualized. Scale bar, 50 µm. Images are representative of three individual mice. (B) Quantification of Artemis-deficient (blue) and -sufficient (red) preB cells in contact with IL-7– and CXCL12-producing cells. Bars indicate mean; circles depict individual mice (n = 3). (C) CXCR4 expression in Artemis-deficient (blue) and -sufficient (red) preB cells in vivo. Numbers indicate geometric mean fluorescence intensity (GMFI) ± SD (n = 3). (D) Il7-GFP expression in nonhematopoietic Lepr+ BM cells of lethally irradiated Il7GFP/+ mice reconstituted with Rag1−/− VH147Igh Eμ-Bcl2 or Dclrec1−/− VH147Igh Eμ-Bcl2 BM cells. (E) Quantification of Il7-GFP expression from D. (F) Geometric mean fluorescence intensity of Il7-GFP expression in nonhematopoietic Lepr+ BM cells of Il7GFP/+ mice 2 wk after transfer of 105 BCR-ABL transduced preB cells. (G) Quantification of Il7-GFP expression from F. (H) Geometric mean fluorescence intensity of Cxcl12-dsRed expression in nonhematopoietic Lepr+ BM cells of Cxcl12dsred/+ Il7GFP/+ mice 2 wk after transfer of 105 BCR-ABL preB cells. (I) Quantification of Cxcl12-dsRed expression from H. Lines indicate mean; circles depict individual mice analyzed (n = 3). (J) Terminal deoxynucleotidyl transferase (Tdt) expression in nonleukemic proB cells isolated from mice described in H. (K) Quantification of terminal deoxynucleotidyl transferase expression from J. (L and M) Total CD19+ host B lymphocytes (L) and granulocytes (M) 2 wk after transfer of 105 BCR-ABL transduced preB cells. (E, G, and K–M) Lines indicate mean; circles depict individual mice analyzed (n = 3). (N) Model of damaged preB or preB-ALL cell/IL-7+ cell circuit. Data in all panels are representative of two to four independent experiments. *, P < 0.05; **, P < 0.01; ***, P < 0.001.

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