The TCL1 protooncogene is overexpressed in many mature B cell lymphomas, especially from AIDS patients. To determine whether aberrant expression promotes B cell transformation, we generated a murine model in which a TCL1 transgene was overexpressed at similar levels in both B and T cells. Strikingly, transgenic mice developed Burkitt-like lymphoma (BLL) and diffuse large B cell lymphoma (DLBCL) with attendant Bcl-6 expression and mutated J H gene segments at a very high penetrance beginning at 4 months of age. In contrast, only one mouse developed a T cell malignancy at 15 months, consistent with a longer latency for transformation of T cells by TCL1. Activation of premalignant splenic B cells by means of B cell antigen receptor (BCR) engagement resulted in significantly increased proliferation and augmented AKT-dependent signaling, including increased S6 ribosomal protein phosphorylation. Transgenic spleen cells also survived longer than wild-type spleen cells in long-term culture. Together these data demonstrate that TCL1 is a powerful oncogene that, when overexpressed in both B and T cells, predominantly yields mature B cell lymphomas.T he TCL1 (T cell leukemia 1) protooncogene is expressed in CD3 Ϫ CD4 Ϫ CD8 Ϫ precursor T cells and is extinguished at the CD4 ϩ CD8 ϩ stage of thymocyte development (1). In B cells, TCL1 is first expressed in pro-B cells and remains high in naive mantle zone B cells of peripheral lymphoid tissues (1-4). Downregulation of TCL1 expression in follicle center centroblasts and centrocytes is followed by gene extinction in post-germinal center (GC) memory B cells and plasma cells (4, 5).Continued high-level TCL1 expression, because of chromosomal rearrangements, was implicated in mature peripheral T cell malignancies (6, 7). Polyclonal and oligoclonal T cell expansions preceded clonal outgrowth by many years, suggesting that additional lesions were required for transformation (8,9). Supporting this tumorigenic mechanism, transgenic mice expressing TCL1-familymember proteins exclusively in T cells developed polyclonal T cell expansions before the evolution of clonal malignancies at 15 to 20 months (10, 11). Overexpression of TCL1, or MTCP1 (mature T cell proliferation 1), in mouse T cells did not affect B cell development or produce B cell lymphomas. These findings indicate that aberrant expression of TCL1 or MTCP1 in T cells perturbs T cell homeostasis through cell autonomous pathways without inducing premalignant or malignant changes in bystander B cells.About 15% of AIDS patients develop aggressive B cell nonHodgkin lymphoma (AIDS-NHL) (12, 13). Most AIDS-NHL originate from GC or post-GC B cells, but the early events leading to AIDS-NHL remain poorly defined (13,14). Diffuse large B cell lymphoma (DLBCL) is the most prevalent type of AIDS-NHL, and these tumors generally lack consistent genetic and͞or viral tumorpromoting alterations. Recently, abundant TCL1 expression was shown in a high percentage of AIDS-NHL of post-GC origin (3,4). This discovery led us to postulate that TCL1 dy...

SUMMARYVirulent classical swine fever (CSF ) represents an immunomodulatory viral infection that perturbs immune functions. Circulatory and immunopathological disorders include leukopenia, immunosuppression and haemorrhage. Monocytic cells -targets for CSF virus (CSFV ) infection -could play critical roles in the immunopathology, owing to their production of immunomodulatory and vasoactive factors. Monocytes and macrophages (Mw) are susceptible to virus infection, as a consequence of which prostaglandin E 2 (PGE 2 ) production is enhanced. The presence of PGE 2 in serum from CSFV-infected pigs correlated with elevated PGE 2 productivity by the peripheral blood mononuclear cells from these same animals. It was noted that these PGE 2 -containing preparations did not inhibit, but actually enhanced, lymphocyte proliferation. The proinflammatory cytokines tumour necrosis factor-a (TNF-a) and interleukin (IL)-6 were not involved, although elevated IL-1 production could relate to lymphocyte activation. Nevertheless, IL-1 was not the sole element: infected Mw produced lympho-stimulatory activity but little IL-1. This release of immunomodulatory factors, following CSFV infection of monocytic cells, was compared with other characteristics of the disease. Therein, PGE 2 and IL-1 production was noted to coincide with the onset of fever and the coagulation disorders typical of CSF. Consequently, these factors are of greater relevance to the haemorrhagic disturbances, such as petechia and infarction, rather than the leukopenia found in CSF.

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