Rearrangement and transcription of the β-chain genes of the T-cell antigen receptor in different types of murine lymphocytes

Kronenberg, Mitchell; Goverman, Joan; Haars, Regina; Malissen, Marie; Kraig, Ellen; Phillips, Lauren; Delovitch, Terry L.; Suciu‐Foca, Nicole; Hood, Leroy

doi:10.1038/313647a0

Cited by 172 publications

(81 citation statements)

References 62 publications

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“…). These results agree with an earlier study that demonstrated that EL4 possessed a partial D␤1-J␤1 rearrangement and expressed a full-length C␤2-containing mRNA transcript (49).…”

Section: El4 and Rma Cell Lines Have A Common Originsupporting

confidence: 83%

The Mouse Tumor Cell Lines EL4 and RMA Display Mosaic Expression of NK-Related and Certain Other Surface Molecules and Appear to Have a Common Origin

Gays

Unnikrishnan

Shrestha

et al. 2000

The Journal of Immunology

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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 CD3ζ 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 TCRβ 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.

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“…). These results agree with an earlier study that demonstrated that EL4 possessed a partial D␤1-J␤1 rearrangement and expressed a full-length C␤2-containing mRNA transcript (49).…”

Section: El4 and Rma Cell Lines Have A Common Originsupporting

confidence: 83%

The Mouse Tumor Cell Lines EL4 and RMA Display Mosaic Expression of NK-Related and Certain Other Surface Molecules and Appear to Have a Common Origin

Gays

Unnikrishnan

Shrestha

et al. 2000

The Journal of Immunology

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“…The simultaneous appearance of both beta 1 and beta 2 rearrange-6.5 Figure 5. Autoradiograph of Southern ments on the same chromosome may be explained by nonproductive Dbeta 2-Jbeta 2 rearrangements (17). SC-5 also demonstrates two beta 1 rearrangements but appears to have one beta 2 rearrangement and a germ-line band.…”

Section: Resultsmentioning

confidence: 99%

T cell receptor beta chain gene rearrangement shared by murine T cell lines derived from a site of autoimmune inflammation.

Padula

Sgroi²,

Lingenheld³

et al. 1988

J. Clin. Invest.

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Advances in our understanding of the structure and molecular biology of the T lymphocyte antigen-receptor have now made it feasible to study human autoimmune diseases using new approaches. One such approach involves cloning of T cells from sites of autoimmune pathology followed by identification of putative disease-related T cell oligoclonality at the level of the T cell receptor gene rearrangements. We have now tested the feasibility of this approach in an animal model of autoimmunity, murine experimental allergic encephalomyelitis (EAE). Spinal cord-derived, self (murine) myelin basic protein (MBP)-reactive T cell lines and sublines were analyzed at the level of their receptor beta chain rearrangements using Southern blots. We now report that the MBP-reactive T cell lines and sublines derived from the spinal cords of four of five SJL/J mice with EAE share a 14.5-kb rearranged T cell receptor beta 1 band on Southern blots. A spinal cord-derived T cell line that was reactive to purified protein derivative of tuberculin (PPD), several lymph node-derived ovalbumin-and PPD-reactive T cell lines, as well as one MBP-reactive spinal cord-derived T cell line did not share this 14.5-kb rearranged beta 1 band. These results suggest that analysis of the antigen receptors used by T cells cloned from sites of inflammation may be a useful initial approach for identifying pathogenetically relevant T cells in the study of certain human autoimmune diseases.

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“…Restriction enzyme digestion to detect rearrangements at the IgH (EcoRI), Igk (BglII), TCR Jb1 (PvuII), Jb2 (HindIII), and Evi3 (XbaI) loci and Southern hybridization have been detailed elsewhere (Gilbert et al, 1993;Justice et al, 1994). Probes for IgH, Igk, TCR Jb1, and Jb2 have been described elsewhere (Kronenberg et al, 1985;Mucenski et al, 1986). The probe for Evi3 was prepared from a 1 kb KpnI genomic fragment cloned into pBluescript KS þ (Justice et al, 1994).…”

Section: Southern Blot Analysismentioning

confidence: 99%

Evi3, a zinc-finger protein related to EBFAZ, regulates EBF activity in B-cell leukemia

et al. 2004

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Retroviral insertions that activate proto-oncogenes are a primary cause of tumors in certain strains of mice. The AKXD recombinant inbred mice are predisposed to a variety of leukemias and lymphomas as a result of viral integration. One common insertion site, the ecotropic viral insertion site 3 (Evi3), has been implicated in most B-cell tumors in the AKXD-27 strain. The Evi3 gene encodes a zinc-finger protein with sequence similarity to the Early B-cell Factor-Associated Zinc-finger gene (EBFAZ). We show that the Evi3 gene is overexpressed in several tumors with viral insertions at Evi3, which results in the upregulation of Early B-cell Factor (EBF)-target gene expression, suggesting that Evi3 modulates EBF activity. Reconstitution of primary leukemia cells showed that these tumors express high densities of the Bcell surface proteins CD19 and CD38, which are EBF targets. Using a transactivation assay, we show that the terminal six zinc-fingers of Evi3 are required for modification of EBF activity. This is the first evidence that Evi3 expression in tumors alters the level of EBF target genes, and the first characterization of the Evi3 protein domains required for modulation of EBF activity. Further, these data imply that Evi3 misexpression initiates tumorigenesis by perturbing B-cell development via an interaction with EBF.

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Rearrangement and transcription of the β-chain genes of the T-cell antigen receptor in different types of murine lymphocytes

Cited by 172 publications

References 62 publications

The Mouse Tumor Cell Lines EL4 and RMA Display Mosaic Expression of NK-Related and Certain Other Surface Molecules and Appear to Have a Common Origin

The Mouse Tumor Cell Lines EL4 and RMA Display Mosaic Expression of NK-Related and Certain Other Surface Molecules and Appear to Have a Common Origin

T cell receptor beta chain gene rearrangement shared by murine T cell lines derived from a site of autoimmune inflammation.

Evi3, a zinc-finger protein related to EBFAZ, regulates EBF activity in B-cell leukemia

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