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 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.
Ponzio
N M
NM
Department of Pathology, UMDNJ New Jersey Medical School and Graduate School of Biomedical Sciences, Newark 07103, USA.
Thorbecke
G J
GJ
D000818:Animals; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology; D051379:Mice; D018089:Superantigens / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
D018089:Superantigens