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Semin Cancer Biol. 2000 Oct;10(5):331-40.

Requirement for reverse immune surveillance for the growth of germinal center-derived murine lymphomas.

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  • 1Department of Pathology, UMDNJ New Jersey Medical School and Graduate School of Biomedical Sciences, Newark 07103, USA.


The concept of reverse immune surveillance, first conceived over 12 years ago, described the relationship that existed between germinal center-derived B cell lymphoma cells and the host immune system in SjL/J mice. According to reverse immune surveillance, recognition of tumor cell antigens and a response by the host immune system is required for tumor growth. The phenomenon of reverse immune surveillance related to B cell lymphomas has recently also been characterized in another inbred mouse strain, C57L/J. Moreover, elements of reverse immune surveillance have been observed in several other mouse strains that develop B cell lymphomas, suggesting that this lymphomagenic mechanism may be more common than first envisioned. In SJL and C57L mice, the B lymphoma cells express an MMTV-encoded superantigen (vSAg29) that stimulates syngeneic CD4+ T cells bearing Vbeta16 in their TCR. In contrast to the mRNAs for other MMTVs in normal mouse B cells, vSAg29 mRNA initiates in the env (META) region, undergoes splicing in the 3' env region, and continues through the 3' LTR. Copious cytokine production, including IFN-gamma, IL-4 and IL-5 accompanies the response of the T cells to this vSAg. In addition to cytokines produced by vSAg-responsive T cells, more recent evidence indicates that another cytokine, LTalphabeta2, which is expressed on the lymphoma cell surface, also plays a role in the promotion of the B cell lymphoma growth. It is possible that interaction with LTbeta-R on follicular dendritic cells or other stromal elements facilitates tumor growth by preventing apoptosis of the malignant B cells. To what degree these findings in the mouse are relevant to the development and/or growth of human B lymphoma cells remains to be determined. However, endogenous retroviral sequences do exist in the human genome. Interestingly, some of these sequences are homologous to MMTV, and are transcribed in B lymphoblastoid cells. Moreover microorganisms that are infectious for human B cells, such as EBV and Herpes Virus 8, may also produce superantigens.

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