Notch2 inhibition is a potential therapeutic strategy in BO-cGVHD without the detrimental side effects characteristic of Notch1 targeting. Following conditioning, B10.BR recipients were transplanted with B6 WT TCD BM cells (10⁷ cells) supplemented with 74 × 10³ B6 WT T cells. Treatment with control vs anti-NRR2 antibodies was given with biweekly injections for 7 weeks, before pulmonary testing was completed. (A) Pulmonary functions tests at day 49 after allo-HCT showing beneficial effects of Notch2 blockade with anti-NRR2 antibodies. (B-C) Anti-NRR2 blockade decreases peribronchiolar collagen deposition in BO-cGVHD. Representative microphotographs of Masson’s trichrome stained lung sections taken at ×200 magnification (B). Cumulative data (C) showing quantification of collagen deposition expressed as a ratio of blue over total stained area. (D-E) Peanut agglutinin staining in the spleens of TCD BM recipients vs recipients of TCD BM plus T cells treated with isotype control or anti-NRR2 antibodies show dampened GC B-cell responses in the spleens of anti-NRR2 treated recipients. Representative microphotographs taken at ×200 magnification (D) and cumulative data (E) quantifying average GC size. *P < .05 (1-way ANOVA).