Figure 1.
BCL6 expression in donor T and B cells is necessary for development of BO cGVHD. B10.BR mice were conditioned with cyclophosphamide (120 mg/kg per day intraperitoneally) on days −3 and −2, and with irradiation (8.3 Gy by radiograph) on day −1 before transplantation. On day 0, mice were transplanted with either TCD B6 BM (BM only) or B6 TCD BM with purified B6 T cells (cGVHD) to establish cGVHD. (A-C) An additional group received TCD BM with BCL6 KO T. (A) Pulmonary function tests, measuring airway resistance, total lung elastance, and compliance were performed on day 56 after transplant. Mice receiving BCL6 KO T cells did not develop pulmonary dysfunction like that of the cGVHD controls. (B) Frequency of splenic GC B cells and TFH cells were analyzed by flow cytometry on day 56 posttransplant. GC B cells and TFH cell frequencies were decreased in the mice that received the BCL6 KO T cells. (C) Collagen deposition as identified by trichrome staining (original magnification ×20) of lung sections harvested day 56 posttransplant. Mice that received KO T cells had reduced collagen deposition in their lungs. (D) Immunoglobulin G (IgG) deposition in lungs of mice that received BCL6 KO T cells was significantly reduced (IgG in Fitc and Dapi; original magnification ×20). (E-H) Transplant was performed as described above with the addition of mice that received either TCD, BCL6fl/fl × CD19-Cre BM (BCL6 KO BM) alone or with purified B6 T cells. cGVHD was assessed as above. (E) Mice that received BCL6 KO BM with WT T cells did not develop pulmonary dysfunction. (F) Frequency of TFH and GC B cells from spleens of mice that received BCL6 KO BM with WT T cells was reduced. (G) Collagen deposition in the lung was decreased in mice that received the BCL6 KO BM with WT T cells (Masson‘s trichrome stain; original magnification ×20). (H) Deposition of IgG in lungs (IgG in Fitc and Dapi; original magnification ×20). Data from 1 experiment with 4 to 6 mice per group. An unpaired Student t test was used when comparing 2 groups. Error bars indicate standard error of the mean (SEM). Significance: *P < .05; **P < .01; ***P < .001.

BCL6 expression in donor T and B cells is necessary for development of BO cGVHD. B10.BR mice were conditioned with cyclophosphamide (120 mg/kg per day intraperitoneally) on days −3 and −2, and with irradiation (8.3 Gy by radiograph) on day −1 before transplantation. On day 0, mice were transplanted with either TCD B6 BM (BM only) or B6 TCD BM with purified B6 T cells (cGVHD) to establish cGVHD. (A-C) An additional group received TCD BM with BCL6 KO T. (A) Pulmonary function tests, measuring airway resistance, total lung elastance, and compliance were performed on day 56 after transplant. Mice receiving BCL6 KO T cells did not develop pulmonary dysfunction like that of the cGVHD controls. (B) Frequency of splenic GC B cells and TFH cells were analyzed by flow cytometry on day 56 posttransplant. GC B cells and TFH cell frequencies were decreased in the mice that received the BCL6 KO T cells. (C) Collagen deposition as identified by trichrome staining (original magnification ×20) of lung sections harvested day 56 posttransplant. Mice that received KO T cells had reduced collagen deposition in their lungs. (D) Immunoglobulin G (IgG) deposition in lungs of mice that received BCL6 KO T cells was significantly reduced (IgG in Fitc and Dapi; original magnification ×20). (E-H) Transplant was performed as described above with the addition of mice that received either TCD, BCL6fl/fl × CD19-Cre BM (BCL6 KO BM) alone or with purified B6 T cells. cGVHD was assessed as above. (E) Mice that received BCL6 KO BM with WT T cells did not develop pulmonary dysfunction. (F) Frequency of TFH and GC B cells from spleens of mice that received BCL6 KO BM with WT T cells was reduced. (G) Collagen deposition in the lung was decreased in mice that received the BCL6 KO BM with WT T cells (Masson‘s trichrome stain; original magnification ×20). (H) Deposition of IgG in lungs (IgG in Fitc and Dapi; original magnification ×20). Data from 1 experiment with 4 to 6 mice per group. An unpaired Student t test was used when comparing 2 groups. Error bars indicate standard error of the mean (SEM). Significance: *P < .05; **P < .01; ***P < .001.

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