Detection of c-rel-related transcripts in mouse hematopoietic tissues, fractionated lymphocyte populations, and cell lines.

Abstract

A portion of the human cellular homolog of v-rel, the transforming gene of the leukemogenic retrovirus reticuloendotheliosis virus, strain T, was used to survey RNAs from several mouse tissues, selected lymphocyte populations, and hematopoietic cell lines for c-rel expression. Relatively high levels of a high-molecular-weight transcript were observed in peripheral B and T cells, whereas lower levels were detectable in functionally immature thymocytes. These results suggested that, unlike c-myb and c-ets, the c-rel proto-oncogene plays a role in later stages of lymphocyte differentiation.REV-T, a highly leukemogenic virus of galliform birds, is believed to have arisen by recombination between a replication-competent type C retrovirus and a portion of a turkey cellular gene designated c-rel (30, 31). Evolutionary comparisons between cloned segments of the turkey and chicken c-rel homologs indicate that the rel locus resembles many other cellular proto-oncogenes in being both large and complex (6, 30). The nine exons from which v-rel was derived, for example, are dispersed over more than 20 kilobase (kb) pairs of DNA and range in size from -60 to over 500 base pairs (30). Very little is known about the normal expression of this cellular gene except that elevated levels of rel-related transcripts can be detected in avian hematopoietic tissues, suggesting a potential role for c-rel in the differentiation of lymphoid and myeloid cell lineages (6,14).Recently, we presented evidence that unique c-rel loci could also be identified in humans, mice, and cats, all of which provide potentially useful genetic model systems for studying the function of this proto-oncogene (3, 4). To date, however, no clear picture has emerged regarding c-rel transcription in any mammalian group, a problem based partly on the fact that the rel-specific probes used in previous studies were derived from the distantly related avian viral rel oncogene (19,23,25,28). In this study, we used a recently described cloned DNA fragment containing two exons of the human c-rel proto-oncogene (4) to screen RNAs from various postnatal mouse tissues, fractionated lymphocytes, and cell lines. We detected large (-7.5 kb) rel-homologous transcripts in thymic and splenic RNAs from 9-, 18-, and 28-day-old mice, whereas RNAs from kidney and liver tissues from the same mice were essentially negative in comparison. Analyses of RNA samples from fractionated lymphocytes showed high levels of rel transcripts in surface immunoglobulin-positive splenic B cells, followed closely by Lyt2-L3T4+ and Lyt2+ L3T4-splenic T lymphocytes. RNA samples from thymocyte populations obtained by differential agglutination with peanut lectin (PNA) were weakly positive, although the more mature, medullary-type PNA-fraction showed a slightly higher level of expression. We corroborated this observation by analyzing RNAs from thymocyte subsets obtained by positive selection and from * Corresponding author.various established murine lymphocyte cell lines. Judging from the elevated levels found i...

Rel-deficient T cells exhibit defects in production of interleukin 3 and granulocyte-macrophage colony-stimulating factor.

“…CD69 (29), CD25/IL-2Ra chain (30), CD44/Pgpl (30), and the Fas/ Apo-1 (CD95) receptor (31,32) are all up-regulated during T-cell stimulation, while L-selectin/CD62 (33) and the CD45 isoform CD45RB (33) (35). Since Rel expression is largely confined to hemopoietic cells (7,8), GM-CSF production was also examined in macrophages from Rel-/-mice. In contrast to the reduced GM-CSF levels secreted by mitogen-stimulated Rel-/-T cells, resident Rel-/-peritoneal macrophages treated with lipopolysaccharide for 24 or 48 hr produce 10-to 50-fold more GM-CSF than normal macrophages (Fig.…”

“…Expression of the Rel subunit is largely confined to hemopoietic cells (7,8). In the B-lymphocyte lineage, increased Rel expression results in a qualitative change in the subunit composition of Rel/NF-KB proteins during the transition from a pre-B to a B cell (9)(10)(11).…”

CD4+ and CD8+ T Cell Survival Is Regulated Differentially by Protein Kinase Cθ, c-Rel, and Protein Kinase B

“…Our data, and those from the B cell studies, indicate that a signaling paradigm linking PKC isoforms to Bcl-x L through the induction of c-Rel may be conserved in cells of lymphoid, and potentially, all of the hemopoietic lineages. This model would fit with the expression of c-Rel, because its expression is confined to the hemopoietic compartment (68,69).…”

Mice lacking the c-rel proto-oncogene exhibit defects in lymphocyte proliferation, humoral immunity, and interleukin-2 expression.

“…In mouse embryos, Rel is first detected at E17, with expression confined to the medullary region of the thymus (Weih et al 1994). Whereas the pattern of Rel expression during murine and avian embryonic development is different, in adult vertebrates, Rel is largely restricted to hemopoietic organs (Brownell et al 1987;Moore and Bose 1989;Grumont and Gerondakis 1990a), with the highest levels in B and T lymphoid cells (Brownell et al 1987;Grumont and Gerondakis 1990a). In the B cell lineage, Rel levels change in a developmental stage-specific manner (Grumont and Gerondakis 1990a).…”