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Published on: October 14, 2016
The mouse tumor cell lines EL4 and RMA display mosaic expression of NK-related and certain other surface molecules
F Gays1, M Unnikrishnan, S Shrestha
1Department of Microbiology, The Medical School, Newcastle, United Kingdom.
Abstract:
As a potential means for facilitating studies of NK cell-related molecules, we examined the expression of these molecules on a range of mouse tumor cell lines. Of the lines we initially examined, only EL4 and RMA expressed such molecules, both lines expressing several members of the Ly49 and NKRP1 families. Unexpectedly, several of the NK-related molecules, together with certain other molecules including CD2, CD3, CD4, CD32, and CD44, were often expressed in a mosaic manner, even on freshly derived clones, indicating frequent switching in expression. In each case examined, switching was controlled at the mRNA level, with expression of CD3zeta determining expression of the entire CD3-TCR complex. Each of the variable molecules was expressed independently, with the exception that CD3 was restricted to cells that also expressed CD2. Treatment with drugs that affect DNA methylation and histone acetylation could augment the expression of at least some of the variable molecules. The striking phenotypic similarity between EL4 and RMA led us to examine the state of their TCRbeta genes. Both lines had identical rearrangements on both chromosomes, indicating that RMA is in fact a subline of EL4. Overall, these findings suggest that EL4 is an NK-T cell tumor that may have retained a genetic mechanism that permits the variable expression of a restricted group of molecules involved in recognition and signaling.
Insights
Mouse tumor cell lines EL4 and RMA show variable expression of NK cell molecules, including CD2 and CD3. This mosaic expression, controlled at the mRNA level, suggests a retained genetic mechanism for molecule switching in these NK-T cell tumors.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- Studies of Natural Killer (NK) cell-related molecules are crucial for understanding immune responses.
- Mouse tumor cell lines provide valuable models for investigating molecular expression patterns.
Purpose of the Study:
- To examine the expression of NK cell-related molecules on various mouse tumor cell lines.
- To investigate the mechanisms underlying variable molecule expression in tumor cells.
Main Methods:
- Screening of mouse tumor cell lines for NK cell molecule expression.
- Analysis of molecule expression patterns, including mosaic expression and switching.
- Investigation of mRNA levels and the role of CD3zeta in CD3-TCR complex expression.
- Assessment of the impact of DNA methylation and histone acetylation inhibitors on molecule expression.
- Genomic analysis of TCRbeta genes to determine the relationship between EL4 and RMA cell lines.
Main Results:
- EL4 and RMA cell lines expressed several NK cell-related molecules (Ly49, NKRP1 families).
- Variable and mosaic expression of NK-related molecules (CD2, CD3, CD4, CD32, CD44) was observed, even in clones, indicating frequent switching.
- Expression switching was regulated at the mRNA level, with CD3zeta controlling CD3-TCR complex expression.
- CD3 expression was dependent on CD2 expression; other molecules varied independently.
- DNA methylation and histone acetylation inhibitors could enhance the expression of some variable molecules.
- EL4 and RMA cell lines were identified as identical, with RMA being a subline of EL4, based on TCRbeta gene rearrangements.
Conclusions:
- EL4 is an NK-T cell tumor exhibiting a unique genetic mechanism for variable expression of recognition and signaling molecules.
- The observed mosaic expression patterns provide insights into NK cell biology and potential therapeutic targets.
- Understanding these expression dynamics is key for advancing NK cell-based immunotherapies.
