Myc/Bcl-X_L PCNs infiltrate the bone marrow, produce monoclonal Ig, and cause osteolytic lesions. (A) Bone marrow infiltration with Igκ-producing neoplastic plasma cells (original magnification, _63). (B) Palisades of neoplastic plasma cells (brown) destroying the luminal face of a femur’s corticalis (IgG immunostaining; original magnification, _40). Two bone resorption lacunae are denoted by arrows. (C) Radiographs of large osteolytic lesion with apparent pathological fracture (1, left humerus), osteolytic lesion without fracture (2, right femur), and hairline fracture without visible osteolytic lesion (3, left forearm). (D) Protein electropherogram of serum and peritoneal lavage samples containing M-spikes (red arrows) isotyped using ELISA (bottom). (E) Frequency and type of mutations in the 3′ JH4 region of rearranged variable (V) genes. Shown at the top is a scheme of the mouse Igh locus. PCR primers J558 and JH4 were used to amplify rearranged VDJ genes and linked 3′JH4 sequences. Sequencing primers iJH4-5′ and iJH4-3′ were used to detect mutations in the 344-bp 3′ JH4 region. Shown in the center are bar diagrams of the number of mutations in the 3′ JH4 region in PCNs and plasmablasts from tumor-free Myc/Bcl-X_L mice (PB, left panel). The corresponding mutation frequencies (mutations/3440 bp) are plotted to the right. Shown at the bottom are types and occurrences of base substitution mutations in the 3′ JH4 region of rearranged VH genes in PCN and PB. The tumor sample also contained a deletion, δT. The location of the mutation in the 3′ JH4 regions is depicted in Supplemental Figure 6.