ML120B-induced B-cell depletion in vivo is TNFR dependent. (A) Representative bone marrow histology and (B) percent cellular decrease in bone marrow and thymus from wild-type control mice (wt), TNFR1-deficient mice, TNFR2-deficient mice, and TNFR1/TNFR2 double knockout mice (R1/R2^–/–) after twice daily oral doses for 3 days (analysis on day 4), with vehicle alone or with ML120B (100 mg/kg). Percent decrease in pre–B cells (B220⁺/IgM^–) and decrease in thymocyte numbers in ML120B-treated animals when compared with vehicle controls (n = 4 per group). (A) Original magnification, 400 × (objective 40 ×/0.75 NA). (C) TNFR1 and TNFR2 expression in bone marrow granulocytes (GR-1⁺). (D) The percent of GR-1⁺ cells expressing TNFR2 but not TNFR1 increases after ML120B dosing. (E) Myeloid progenitors (CFUs) surviving 3 days of ML120B dosing are not resistant to ML120B + TNFα killing in vitro. Bone marrow cells from individual mice (n = 4) were cultured in media or ML120B (30 μM) in the presence of murine TNFα (100 ng/mL) for 4 hours then washed and plated in culture conditions for myeloid colony growth. Colonies were scored 7 days after plating. All cultures contained 0.5% DMSO.