Figure 2. Overexpression of BATF3 in mature B cells results in lymphomagenesis.

(A) Experimental design and transplantation model. Wild type (WT) C57BL/6 mice were used as donors for mature B and T cells. Isolated cells were stimulated in cell culture, retrovirally transduced and transplanted into Rag1-deficient recipient mice. B-cells were co-transplanted with freshly isolated, TCR quasi-monoclonal, CD4⁺ T cells from OT-II mice. Mice were monitored by blood sampling and monitored for lymphoma development. (B) Survival of T- and B-cell transplanted recipients. Cohorts transplanted with BATF3-expressing B cells (black solid and dotted lines) developed lymphomas after different latencies. Animals that received highly BATF3-transduced B cells (black solid line) succumbed earlier to lymphoma than recipients of low BATF3-expressing B cells (black dotted line). One of the mice transplanted with cells transduced with high levels of BATF3 vector died of lymphoma, but could not be included in the detailed characterization of the lymphomas because of insufficient quality of the necrotic tissue. Recipients of BATF3-expressing T cells and EGFP-control cells did not show any signs of malignancy during the observation period (gray lines). (C) Representative histologies of a BATF3-induced B-cell lymphoma. Necropsy of diseased animals revealed massive infiltration of tumor cells into the liver, spleen and lymph nodes. Hematoxilin and eosin stained tumors demonstrated blastoid infiltrates and a destruction of the normal, organ-specific architecture. Bars represent 100 μm. (D) Representative immunohistochemical stainings of BATF3-induced tumors. Sections of tumor-infiltrated spleen of BATF3-induced lymphomas were stained for the B-cell marker CD79b and the GC B-cell markers BCL6 and PNA. Bars represent 100 μm.