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

The concept of reverse immune surveillance, first conceived over 12 years a go, 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 re sponse by the host immune system is required for tumor growth. The phenomen on of reverse immune surveillance related to B cell lymphomas has recently also been characterized in another inbred mouse strain, C57L/J. Moreover, e lements of reverse immune surveillance have been observed in several other mouse strains that develop B cell lymphomas, suggesting that this lymphomag enic mechanism may be more common than first envisioned. In SJL and C57L mice, the B lymphoma cells express an MMTV-encoded superant igen (vSAg29) that stimulates syngeneic CD4(+) T cells bearing beta 16 in t heir 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 productio n, including IFN-gamma, IL-4 and IL-5 accompanies the response of the T cel ls to this vSAg. In addition to cytokines produced by vSAg-responsive T cel ls, more recent evidence indicates that another cytokine, LT alpha beta2, w hich is expressed on the lymphoma cell surface, also plays a role in the pr omotion of the B cell lymphoma growth. It is possible that interaction with LT beta -R on follicular dendritic cells or other stromal elements facilit ates 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 infections for huma n B cells, such as EBV and Herpes Virus 8, may also produce superantigens.