Figure 1.
VavP-Bcl2 transgenic mice develop follicular lymphoma. (A) Histopathology of lymphoma in a 335-day-old VavP-Bcl2 45 mouse, which had massive enlargement of the spleen and lymph nodes and extensive infiltration of the liver and kidneys. Low-power (× 10) views of spleen and a lymph node (left) show nodular and diffuse infiltration, and a section of the liver (middle) with extensive infiltrates in the portal tract. High-power (× 100) view of the tumor tissue (right) shows centrocytes, with their small, darkly stained nuclei, among the larger centroblasts with their typical vesicular nucleus containing a prominent nucleolus and dispersed chromatin. (B) Cumulative incidence of follicular lymphoma in VavP-Bcl2 transgenic mice. A total of 69, 40, and 49 mice of strains 45, 68, and 69, respectively, were monitored up to 18 months of age. Follicular lymphoma was diagnosed from histology of enlarged lymphoid organs of sick mice. The incidence in each strain was determined by censoring all cases of other disease at the time of occurrence, as well as any mice removed for analysis. There were no significant differences among the 3 strains by log-rank test (chi-square = 0.651; P = .722). (C) Rearranged immunoglobulin VDJ sequences were amplified as described in “Materials and methods” and analyzed at high resolution in an automated sequencer. Control B cells sorted from healthy C57BL/6 spleen yielded, as expected, multiple clusters of bands separated by 3 base pairs. The 3 lower panels show VDJ genes from individual follicular lymphomas, each yielding a single predominant band indicative of clonality.