Notch signaling mediated by Dll1 and Dll4 is necessary for the development and persistence of BO-cGVHD. B10.BR recipients were conditioned with total body irradiation (8.3 Gy, day −1) and cyclophosphamide (120 mg/kg/day i.p., days −3 and −2) before transplantation with B6 WT TCD BM only (10⁷ cells) vs TCD BM plus 80 × 10³ B6 WT or B6-DNMAML T cells. (A) Pulmonary function testing (resistance, elastance, and compliance) was performed at day 56 after allo-HCT. Recipients of WT, but not DNMAML, T cells showed profound changes consistent with BO-cGVHD airway disease. *P < .05 (1-way ANOVA). (B) B10.BR recipients were transplanted as indicated above. After 4 weeks, systemic treatment was started with isotype control vs anti-Dll1, anti-Dll4, or a combination of anti-Dll1 and anti-Dll4 antibodies (5 mg/kg i.p. twice weekly, days 28-56). Pulmonary function tests were performed at day 56. *P < .05 for mice treated with isotype control antibodies (BO-cGVHD) vs mice receiving only TCD BM (GVHD-free control) and all groups receiving Notch ligand neutralizing antibodies. (C) Dll1 and/or Dll4 inhibition alters GC B-cell homeostasis, significantly decreasing the frequency of B cells with a GL7⁺Fas^hi GC B-cell phenotype in the spleen. *P < .05. Representative data from one of 2 experiments is shown with 8 animals per group.