Rearrangement of rat immunoglobulin E heavy-chain and c-myc genes in the B-cell immunocytoma IR162.

Tian, Shin-Shay; Faust, Charles

doi:10.1128/mcb.7.7.2614

Cited by 13 publications

(4 citation statements)

References 14 publications

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“…The finding that £ producers show recombination between the c-myc and switch e region suggests that there is an apparent relationship between isotypic expression and the c-myc translocation target. A study of the IgE-secreting IR162 also showed that the c-myc recombines with the switch £ region (54); however, as demonstrated by our study of the IgE-producing IR75 (34), not all IgE-secreting RICs show juxtaposition between the c-myc and switch £.…”

Section: Discussion Of 16mentioning

confidence: 45%

6;7 chromosomal translocation in spontaneously arising rat immunocytomas: evidence for c-myc breakpoint clustering and correlation between isotypic expression and the c-myc target.

Pear¹,

Wahlström²,

Nelson³

et al. 1988

Mol. Cell. Biol.

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Our previous studies have shown that spontaneously arising immunocytomas in the LOU/Wsl strain of rats contain a t(6;7) chromosomal translocation in all seven tumors studied (F. Wiener, M. Babonits, J. Spira, G. Klein, and H. Bazin, Int. J. Cancer 29:431-437, 1982). We have also shown that the c-myc is located on chromosome 7 (J. Sumegi, J. Spira, H. Bazin, J. Szpirer, G. Levan, and G. Klein, Nature (London) 306: [497][498][499] 1983) and the immunoglobulin H cluster on chromosome 6 (W. S. Pear, G. Wahistrom, J. Szpirer, G. Levan, G. Klein, and J. Sumegi, Immunogenetics 23:393-395, 1986). We now report a detailed cytogenetic and molecular analysis of nine additional rat immunocytomas. The t(6;7) chromosomal translocation is found in all tumors. Mapping of the c-myc breakpoints showed that in 10 of 14 tumors, the c-myc breakpoints are clustered in a 1.5-kilobase region upstream of exon 1. In contrast with sporadic Burkitt's lymphoma and mouse plasmacytoma, only 1 of 14 tumors contains the c-myc breakpoints in either exon 1 or intron 1. Analysis of the sequences juxtaposed to the c-myc show that immunoglobulin H switch regions are the targets in at least five tumors and that there is a strong correlation between the secreted immunoglobulin and the c-myc target. Unlike sporadic Burkitt's lymphoma and mouse plasmacytoma, at least two rat immunocytomas show recombination of the c-myc with sequences distinct from immunoglobulin switch regions.Consistent chromosomal translocations are thought to play an important role in the development of certain neoplasms (10, 21). The role of specific translocations has been extensively studied in two B-cell tumors, Burkitt's lymphoma (BL) and mouse plasmacytoma (MPC), and chromosomal translocations have been identified in 100% of the former and 95% of the latter type of tumor (22). BL and MPC represent different stages of B-cell maturation; however, the chromosome translocation in both tumors involves the chromosomes containing one of the immunoglobulin loci and the c-myc cellular oncogene (23). The translocation is believed to act by constitutive activation of c-myc (9). Recent facsimile experiments have shown that constitutively activated c-myc genes can induce tumors in an appropriate host environment (1,24,27

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Section: Discussion Of 16mentioning

confidence: 45%

6;7 chromosomal translocation in spontaneously arising rat immunocytomas: evidence for c-myc breakpoint clustering and correlation between isotypic expression and the c-myc target.

Pear¹,

Wahlström²,

Nelson³

et al. 1988

Mol. Cell. Biol.

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“…LPS treatment of normal spleen cells induces the appearance of cells that have switched to y2b (and y3) production, whereas treatment of these normal cells with IL-4 plus LPS abrogates the appearance of y2b-producing cells, but now stimulates the appearance of cells that produce a (and yl) (7,14,39 (21). In striking contrast, we demonstrate that treatment of splenic lymphocytes with LPS alone has absolutely no effect on the expression of the germ line E transcription unit (and switching to e), whereas treatment with IL-4 plus LPS dramatically induces germ line E transcripts in these cells followed by switching to e. There is substantial evidence that switch region rearrangement is a major pathway in the production of IgE in such systems (15,23,32,37). Therefore, our findings provide strong support for the notion that expression of germ line transcripts by B lineage cell lines is directly related to factors involved with directing the class-switch process.…”

Section: Resultsmentioning

confidence: 57%

Structure and expression of germ line immunoglobulin heavy-chain epsilon transcripts: interleukin-4 plus lipopolysaccharide-directed switching to C epsilon.

et al. 1990

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We have isolated cDNA clones complementary to a truncated immunoglobulin heavy-chain Ca RNA transcript previously found to be induced in B lymphoid cells by treatment with lipopolysaccharide (LPS) combined with interleukin-4 (IL-4). We demonstrate that this transcript initiates from a promoter upstream of the germ line £ class-switch recombination region (Sa region). The major germ line Ca transcript contains a small 5' exon contributed by sequences upstream of the SE region spliced to the normal CE exons. Treatment of splenic B lymphoid cells with LPS plus IL-4 induces the expression of transcripts from the germ line transcription unit followed by expression of normal immunoglobulin heavy-chain mRNA. Furthermore, we demonstrate that similar treatment of transformed precursor B cell lines induces the expression of germ line transcripts followed by class switching to expression in these lines. This is the first demonstration of switching to in cells of the pre-B stage. The general structure of the germ line transcript and transcription unit is similar to that previously characterized for germ line -y2b transcripts. However, expression of these two germ line transcription units in B-lineage cells is inversely regulated by IL-4 (plus LPS) treatment, correlating with the effects of these treatments on switching to these loci.Immunoglobulin molecules consist of a pair of identical heavy (H) lead to production of antibodies with distinct CH subsets. For example, high levels of IgG2a occur during murine viral infections (10). In contrast, murine parasitic infections lead to high-level IgE production (16). Recent work has indicated that lymphokines secreted by T lymphocytes influence which CH genes are produced by B cells (reviewed in references 8 and 24), perhaps as a result of a direct influence on the class-switch process (21).The role of external agents in regulating immunoglobulin isotype production has been studied by using cell culture systems in which B lymphocytes are polyclonally activated with compounds such as bacterial lipopolysaccharide (LPS) along with purified lymphokines. Splenic lymphocytes cultured with LPS produce, in addition to >i, large amounts of -y2b and y3 (45); when the T cell lymphokine interleukin-4 (IL-4) is added to LPS cultures, levels of -y2b and y3 decrease, while production of E and -yl increases (reviewed in references 24 and 25). These responses occur, at least in large part, due to outgrowth of B-lineage cells that have undergone recombination-deletion class-switch events (26,40). The propensity of normal and transformed B-lineage cells to switch to certain H-chain isotypes may be correlated with expression of the corresponding germ line CH gene (reviewed in reference 27). For

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“…A specific mechanism to recombine S regions appears to exist in B lineage cells (7). The frequent occurrence of recombination events to the same S region on the two alleles of plasmacytomas, immunocytomas, and normal B cells suggests that class switching may not be a random process (4,11,13). 1.29 B lymphoma cells produce Ce,-, C8-and Cy2a-hybridizing transcripts prior to switching to these CH genes (10), and Abelson murine leukemia virus (A-MuLV)-transformed pre-B cell lines express Cy2b-hybridizing transcripts prior to switching to y2b (14), leading to the idea that directed switching could be achieved by modulating the accessibility of a given S region to a common S recombinase (10,14).…”

mentioning

confidence: 99%

Structure and expression of germ line immunoglobulin gamma 2b transcripts.

1988

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We have isolated a cDNA copy of a truncated C gamma 2b transcript produced by Abelson murine leukemia virus transformants that spontaneously switch from mu to gamma 2b. The initiation site of this transcript was 2 kilobases 5' to the gamma 2b switch recombination region, demonstrating its germ line origin. Nucleotide sequence analyses suggest that this transcript does not encode a protein. Expression of germ line gamma 2b transcripts in Abelson murine leukemia virus transformants and in normal spleen cells correlated with endogenous gamma 2b class switch activity.

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Rearrangement of rat immunoglobulin E heavy-chain and c-myc genes in the B-cell immunocytoma IR162.

Cited by 13 publications

References 14 publications

6;7 chromosomal translocation in spontaneously arising rat immunocytomas: evidence for c-myc breakpoint clustering and correlation between isotypic expression and the c-myc target.

6;7 chromosomal translocation in spontaneously arising rat immunocytomas: evidence for c-myc breakpoint clustering and correlation between isotypic expression and the c-myc target.

Structure and expression of germ line immunoglobulin heavy-chain epsilon transcripts: interleukin-4 plus lipopolysaccharide-directed switching to C epsilon.

Structure and expression of germ line immunoglobulin gamma 2b transcripts.

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