Antibody-producing donor B cells are not required to initiate tissue damage, but they are required for persistence of tissue damage. BALB/c recipients were lethally irradiated (850 cGy TBI) and given high-dose (75 × 10⁶) and low-dose (25 × 10⁶) CD25-depleted splenocytes and TCD-BM (2.5 x10⁶) cells from WT or IgH^μγ1 DBA/2 donors. Recipients given TCD-BM (2.5 × 10⁶) from WT or IgH^μγ1 DBA/2 donors alone were combined and used as negative controls for GVHD. Recipients were monitored for GVHD development, including proteinuria, clinical cutaneous GVHD, and survival († indicates death of all recipients in a group). (A) Percentage of mice without proteinuria, clinical cutaneous GVHD score, and percentage of survival; N = 8 from 2 replicate experiments. (B) On day 40 after HCT, histopathology of the GVHD target tissues liver, lung, salivary gland, and skin, and antibody deposition in the skin was evaluated. A representative photomicrograph (original magnification ×200 for histopathology and ×100 for IgG deposition); means ± standard error (SE) (N = 6) of histopathology scores are shown. Arrows indicate the following: infiltration in the liver, lymphocytic bronchiolitis, infiltration and loss of ductal structure in the salivary gland, and hyperplasia in the epidermis, expansion of dermis, and loss of subcutaneous fat. Antibody deposition in the skin was quantified by the intensity of anti-mouse IgG–fluorescein isothiocyanate (FITC) in 5 different levels of 4 examined mice at each group. (C) On day 60 after HCT, histopathology of the GVHD target tissues liver, lung, salivary gland, skin, and antibody deposition in the skin was evaluated. A representative photomicrograph (original magnification, ×200 for histopathology and ×100 for IgG deposition); means ± SE (N = 6) of histopathology scores or means ± SE (N = 4) of anti-IgG–FITC intensity are shown. Arrows are described in panel B (**P < .01, ***P < .001, ****P < .0001).