Figure 1

Manifestation and histopathological features of lymphoproliferative disease in BCL2⁺IL6⁺AID⁻ mice. (a) Generation of BCL2⁺IL6⁺AID⁻ mice. The human BCL2 transgene EμSV-BCL2-22 (BCL2⁺) and human IL6 transgene H2-L^d-hIL6 (IL6⁺) were transferred to the Aicda null background of AID deficiency (AID⁻) using the breeding scheme depicted in Supplementary Figure 1. AID-proficient, double-transgenic BCL2⁺IL6⁺AID⁺ mice, generated by intercrossing strains BCL2⁺ and IL6⁺, were used as controls. Both transgenes and the Aicda null allele were on the genetic background of BALB/c (C), which is highly susceptible to malignant plasma cell transformation. (b) Kaplan–Meier curve showing tumor free survival of AID-deficient BCL2⁺IL6⁺AID⁻ mice (red curve) and AID-proficient BCL2⁺IL6⁺AID⁺ mice (black curve). (c) Necropsy photographs of a diseased BCL2⁺IL6⁺AID⁻ (left) and BCL2⁺IL6⁺AID⁺ (right) mouse. Some grossly enlarged lymph nodes (LNs) are labeled. (d) Photomicrograph of BCL2⁺IL6⁺AID⁻-dependent lymphoproliferation after staining with hematoxylin and eosin (H&E; original magnification 63x). Mitotic figures are circled yellow. Aberrant centroblast-like and immunoblast-like B cells are indicated by yellow arrowheads pointing right and left, respectively.