| Autor: |
Gomez, Gregorio, Clarkin, Kimberly Z., Kraig, Ellen, Infante, Anthony J., Richie, Ellen R. |
| Zdroj: |
International Immunology; Mar2000, Vol. 12 Issue 3, p263-270, 8p |
| Abstrakt: |
Thymic lymphoma development is a multistage process in which genetic and epigenetic events cooperate in the emergence of a malignant clone. The notion that signaling via TCR–ligand interactions plays a role in promoting the expansion of developing neoplastic clones is a matter of debate. To investigate this issue, we determined the TCR Vβ repertoire of thymic lymphomas induced in AKR/J mice by either endogenous retroviruses or the carcinogen, N-methyl-N-nitrosourea (MNU). Both spontaneous and MNU-induced lymphomas displayed restricted Vβ repertoires. However, whereas Vβ6, Vβ8 and Vβ9 were expressed by a greater than expected frequency of MNU-induced lymphomas, Vβ8, Vβ7, Vβ13 and Vβ14 were over-represented on spontaneous lymphomas. The dissimilar TCR Vβ profiles indicate that different endogenous ligands promote neoplastic clonal expansion in untreated and MNU-treated mice. Although the nature of these ligands is not clear, the lack of conservation in TCR β chain CDR3 regions among lymphomas that express the same Vβ segment suggests that endogenous superantigens (SAG), as opposed to conventional peptide ligands, are likely to be involved in the selection process. The biased representation of lymphomas expressing Vβ6-, Vβ7- and Vβ9-containing TCRs that recognize endogenous SAG is consistent with this hypothesis. The finding that Bcl-2 is expressed at high levels in spontaneous and MNU-induced lymphomas suggests that preneoplastic thymocytes may be resistant to SAG-induced clonal deletion. A working model is presented in which preneoplastic clones expressing TCRs that recognize endogenous SAG are selectively expanded as a consequence of sustained TCR-mediated signaling. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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