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At least 433 records · Page 24Linked to original sources
PubMed2003

Differential expression of Ran GTPase during HMBA-induced differentiation in murine erythroleukemia cells.

Murine erythroleukemia (MEL) cells undergo erythroid differentiation in vitro when treated with hexamethylene bisacetamide (HMBA). To identify genes involved in the commitment of MEL cells to differentiate, we screened a cDNA library constructed from HMBA-induced cells by differential hybridization and isolated GTPase Ran as a down-regulated gene. We observed that Ran was expressed in a biphasic mode. Following a decrease in mRNA level during the initial hours of induction, Ran re-expressed at 24-48 h, and gradually declined again. To investigate the role of Ran during MEL differentiation we constructed MEL transfectants capable to express or block Ran mRNA production constitutively. No effects were observed on cell growth and proliferation. Blockage of Ran, however, interfered with MEL cell differentiation resulting in a decrease of cell survival in the committed population.

Acetamides↗
PubMed1999

Differential expression of glutaredoxin and thioredoxin during monocytic differentiation.

Macrophages generate reactive oxygen intermediates (ROIs) as the effectors of anti-bacterial defense mechanism. Intracellular ROIs and reduction/oxidation (redox) status play crucial roles in signal transduction. We therefore investigated the expression of redox-regulating proteins such as glutaredoxin (GRX) and thioredoxin (TRX) during the differentiation of murine monocytic leukemia cell line M1 cells and human monocytic leukemia cell line U937 cells. When M1 cells were treated by IL-6, GRX mRNA markedly increased and TRX mRNA also increased slightly. In contrast, there was no increase of GRX mRNA in D-cell, which is a sub-cell line derived from M1 lacking in the capacity of differentiation. GRX mRNA also increased in U937 cells differentiated by phorbol 12-myristate 13-acetate (PMA). By immunohistochemistry, unstimulated M1 cells showed strong staining of TRX and marginal staining of GRX. In contrast, TRX expression in IL-6 treated M1 cells is as strong as in unstimulated M1 cells, whereas GRX expression is slightly enhanced in IL-6 treated M1 cells. Phagocytosis is markedly enhanced and hydrogen peroxide production is slightly enhanced in IL-6 treated M1 cells. These results showed that TRX is steadily expressed whereas GRX is induced in association with the differentiation in macrophage-like cell line cells, suggesting differential roles of these redox regulators in macrophage lineage.

Animals↗
PubMed2001

Differential localization of the neurofibromatosis 1 (NF1) gene product, neurofibromin, with the F-actin or microtubule cytoskeleton during differentiation of telencephalic neurons.

The protein product of the neurofibromatosis 1 gene, neurofibromin, is abundantly expressed in the cerebral cortex during development, but its physiological role remains unknown. To gain insights into the functions of neurofibromin in neurons, we examined patterns of expression and subcellular localization of neurofibromin during neuronal differentiation. Western blot analysis of telencephali homogenates throughout chick embryogenesis revealed that neurofibromin expression increased during embryonic development. Further analysis showed that telencephalic neurons were also enriched in neurofibromin in culture and that a biphasic gain in expression correlated well with both phases of differentiation in culture, first with a massive outgrowth of processes and gains in neurotransmitter phenotype differentiation, and then with synapse formation. Compared to proteins associated with distinct cytoskeleton systems, the pattern of neurofibromin expression correlated closely with that of the cortical cytoskeleton protein paxillin. Moreover, analysis of immunofluorescence staining of neurofibromin showed that in the presence of a protein crosslinker which preserves both soluble and filamentous cytoskeleton proteins after extraction with Triton X-100, neurofibromin colocalized with F-actin only during the first differentiation phase. This colocalization persisted when the actin cytoskeleton was collapsed with cytochalasin D treatment. In contrast, during the second phase of differentiation neurofibromin colocalized with microtubules, but not F-actin, and the staining pattern was disrupted with nocodazole, but not cytochalasin. A constant finding under all conditions was the presence of neurofibromin in the nucleus, which supports the idea that the bipartite nuclear targeting sequence between residues 2555 and 2572 of neurofibromin may be functional. In summary, we have shown that telencephalic neurons and astroblasts are enriched in neurofibromin and that the subcellular targeting of neurofibromin toward the actin or the microtubule cytoskeleton is developmentally regulated.

Actin Cytoskeleton↗
PubMed2001

Low-density cDNA array-coupled to PCR differential display identifies new estrogen-responsive genes during the postnatal differentiation of the rat hypothalamus.

To identify estrogen (E)-responsive genes that may play important roles in the sexual differentiation and maturation of the neuroendocrine hypothalamus, we used mRNA differential display PCR to analyze hypothalamic RNA derived from estrogen-sterilized rats (ESRs). Neonatal rats were s.c.-injected with 100 microg of 17 beta-estradiol-benzoate (EB) for 5 days. Approximately 300 out of more than 2000 RNAs examined displayed a differential expression pattern between hypothalami of the ESR females compared to their 60-day-old controls. EB-dependent expression of these genes was further analyzed by low-density cDNA array using cDNA probe sets reverse-transcribed from the same groups; 98 genes were confirmed to be differentially expressed. We selected 41 clones that showed higher density differences between the two probe sets than mean density difference in control cyclophilin cDNA blots in the cDNA array. After being cloned into pGEM-T vectors, their sequences were analyzed. Homology searches identified four genes as a protein kinase C (PKC)-binding protein, NELL2 (clone 6-1), a thyroid nuclear factor, TTF-1 (9-1), Munc18-1 (17-6), and leuserpin-2 (18-5). The other 22 genes were similar to reported genes or cDNAs such as mouse kinesin-associated protein 3 (KAP3, 8b), mouse IgE binding lectin (15-1), normalized rat brain cDNA (5-1), rat cDNA (8-1) and rat embryonic cDNA (17-1). Fifteen clones such as clone 7-3 showed no match in the GenBank Database. Further characterization of eight clones (17-1, 7-3, 8-1, 5-1, NELL2, KAP3 homolog, IgE binding lectin homolog, and TTF-1) showed that their expression in the adult female rat hypothalamus is sensitive to neonatal treatment with EB. They showed brain-specific expression and moreover, showed an increase in their mRNA level before the initiation of puberty. Some of them showed gender differences in their different postnatal expression pattern. We speculate that further study will demonstrate that many of the E-regulated genes identified in the present study play important roles in the regulation of the sexual differentiation and E-dependent maturation of the hypothalamus.

Animals↗
PubMed1999

Differential effect on U937 cell differentiation by targeting transcriptional factors implicated in tissue- or stage-specific induced integrin expression.

The inhibition of transcription factor functions was used to define their role in phorbol ester-induced cellular differentiation of a monocytic cell line, U937. We demonstrate a differential effect on cell adhesion and differentiation: antisense or competitive binding with double-stranded oligonucleotides antagonized the functions of AP-1, NF-kappaB, and PU.1 transcriptional factors. In the presence of phorbol 12-myristate 13-acetate (PMA), U937 cells attached to the plastic surface and cells were characterized by marked expression of beta2-integrin molecules on the cell surface. We show that the in vivo differentiation of U937 cells appears to occur normally in the absence of AP-1 activity. In contrast, the addition to the cell culture of phosphorothioate oligonucleotides that contained the NF-kappaB or PU.1 binding sites significantly inhibited U937 differentiation. The absence of NF-kappaB led to pleiotropic effects with a clear reduction in the expression of integrin and other lineage-specific myeloid antigens on the cell surface. In contrast, the absence of PU.1 had a more restricted effect on integrin expresion on the cell surface, probably as a result of blockage of CD18 gene expression.

CD18 Antigens↗
PubMed1997

Fluorescent differential display analysis of gene expression in differentiating neuroblastoma cells.

Identification of differentially-expressed genes provides an important step toward the elucidation of molecular mechanisms underlying a variety of biological processes. A novel PCR-based approach to detect and clone such transcripts is the so-called differential display (DD). We established an improved DD protocol that can be performed on an automated fluorescent DNA sequencer to ensure high throughput as well as operational safety. Using this fluorescent DD (FDD) technique, we analyzed the gene expression profile in the retinoic acid-induced differentiation of a human neuroblastoma cell line SH-SY5Y. Screening with 102 primer combinations at eight different time points revealed 66 cDNA bands with variously different behaviors out of approximately 6000 bands displayed. Subsequent analyses with 15 cloned species confirmed the differential expression of corresponding transcripts in all the cases, thereby demonstrating the high reliability of FDD analysis. These clones were composed of seven novel and eight known genes, the latter of which included those that had never been described in the context of neuronal differentiation. These results indicate that FDD is an effective approach to obtain not only novel genes but also clues to possible novel functions of known genes involved in various biological phenomena.

Amino Acid Sequence↗
PubMed2001

Characterisation of Wnt gene expression during the differentiation of murine embryonic stem cells in vitro: role of Wnt3 in enhancing haematopoietic differentiation.

The first haematopoietic stem cells in mammalian and non-mammalian vertebrates are derived from mesoderm, therefore genes that are important in mesoderm patterning and formation might also play an essential role in haematopoietic stem cell commitment and differentiation. Several members of the Wnt gene family are expressed in very specific patterns in embryonic mesoderm and have previously been shown to act as haematopoietic growth factors. In order to investigate in detail the role that such secreted proteins play in the biology of early haematopoietic commitment we have used in vitro differentiation of murine embryonal stem (ES) as a model system. Using reverse-transcriptase polymerase chain reaction analysis we identified several candidate Wnt genes whose expression pattern was consistent with a role in generation, maintenance and/or differentiation of early haematopoietic progenitor cells including three genes previously shown to have a role in haematopoiesis (Wnt5a, Wnt2b and Wnt10b). The most interesting candidate was Wnt3, because of its strong and regulated expression during in vitro differentiation of murine ES cells as well as its early embryonic expression in mesoderm. Overexpression of Wnt3 was sufficient to cause a consistent increase in the number of embryoid bodies committing to haematopoiesis further strengthening the evidence that this protein can enhance haematopoietic commitment during in vitro differentiation of ES cells. In addition, overexpression of Wnt3 caused a marked upregulation of Brachyury expression, thus providing some evidence that Brachyury may be one of the target genes for the Wnt3 signalling pathway.

Animals↗
PubMed1997

Differential effect of components of the extracellular matrix on differentiation and apoptosis.

BACKGROUND: Epithelial cells are closely associated with a basement membrane, but the intimate relationships that affect growth, differentiation and survival remain enigmatic. We have previously reported that granulosa cells adjacent to the basement membrane of the ovarian follicle have a higher degree of differentiation compared with cells located distal to the basement membrane. By contrast, granulosa cells distal to the basement membrane are the first to undergo apoptosis during follicular atresia. Moreover, growth of granulosa cells in vitro on a naturally produced basement-membrane-like extracellular matrix (ECM) enhances progesterone production and the cellular response to gonadotropic hormones by an undefined mechanism. RESULTS: To investigate the effect of the ECM on granulosa cell differentiation and death, primary granulosa cells were cultured on ECMs that lacked or contained bFGF (basic fibroblast growth factor). These otherwise identical ECMs were deposited by HR9 mouse endodermal cells, which do not synthesize bFGF, or by HR9 cells transfected with the bFGF gene. Both ECMs provided protection against apoptosis in serum-free medium, but only the bFGF-containing ECM maintained expression of the steroidogenic P450scc enzyme system and the production of progesterone. Moreover, culturing the cells on this ECM enhanced the expression of the 30 kDa steroid acute regulatory protein which plays a key role in steroid hormone biosynthesis. Laminin, but not fibronectin, was able to replace the ECM in protecting the cells from apoptosis; but not in maintaining steroidogenesis, whereas bFGF was able to enhance steroidogenesis without protecting the cells against apoptosis. Cells cultured on both ECMs or laminin had a well-developed actin cytoskeleton compared with cells cultured on non-coated dishes, which underwent apoptosis. CONCLUSIONS: Cellular responses to ECM are mediated by the combined action of macromolecular constituents and regulatory molecules, such as bFGF, that are sequestered and stored in the ECM. ECM or laminin protects against cell death by interacting with specific integrin receptors and maintaining a well-developed actin cytoskeleton. ECM-bound bFGF provides differentiation signals for granulosa cells, which are in intimate contact with the ECM. Thus, a clear distinction can be made between the survival activity and the differentiation stimulus exerted by the ECM on epithelial cells.

Actins↗
PubMed2002

Differential effects of three inhibitors of glycosphingolipid biosynthesis on neuronal differentiation of embryonal carcinoma stem cells.

Gangliosides have been implicated in having important roles in neural development. It has been shown that disruption of ganglioside biosynthesis inhibits neurite outgrowth. However, many contradictory results have been reported. The inconsistency of these reports may result from the differential use of neuronal cell lines and inhibitors for ganglioside biosynthesis. In order to clarify the inconsistency in these studies, we utilized an in vitro neuronal differentiation model using an embryonic caricinoma (EC) stem cell line to elucidate the relationship between ganglioside expression and neural development. These cells were exposed to three different inhibitors of glucosylceramide synthase, the first enzyme committed for the biosynthesis of most of the brain gangliosides. All three inhibitors, D-threo-1-phenyl-2-decanoylamino-3-morphlino-1-propanol (D-PDMP), D-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (D-PPPP), and N-butydeoxynojirimycin (NB-DNJ) can inhibit greater than 90% of ganglioside biosynthesis at certain concentrations, respectively. D-PDMP significantly slowed down cellular proliferation in undifferentiated P19 EC cells, inhibited neurite outgrowth, and eventually caused cell death in differentiated cells. However, no retardation in cell growth, neuronal differentiation, and neurite outgrowth was observed in cultures treated with D-PPPP or NB-DNJ despite the depletion of gangliosides. These results indicate that the effect of D-PDMP on cellular proliferation, neurite outgrowth, and survival of differentiated cells is independent of the inhibition of ganglioside biosynthesis.

Animals↗
PubMed2025

Nfe2l1 dysfunction alters Parkinson's disease-related gene expression and impairs neuronal differentiation under ubiquitin stress in neuronal differentiated P19 Cells.

Proteostasis is essential for neuronal health, and its disruption is implicated in neurodegenerative diseases such as Parkinson's disease (PD). Nfe2l1, a key regulator of proteostasis and ubiquitination, plays a significant role in neuronal health, yet its molecular functions in neuronal cells remain unclear. Our study investigates the role of Nfe2l1 in RA-induced neuronal differentiation of P19 cells under proteasome inhibition. This condition significantly increased Nfe2l1 expression at both protein and RNA levels in wild-type and differentiated cells. In differentiated cells under proteasome inhibition, RNA sequencing revealed an enrichment of neurodegenerative pathways, particularly those associated with PD. Proteasome inhibition led to the upregulation of several PD-related genes, including Atf6, Camk2d, and Sod1. However, Nfe2l1 knockdown in differentiated cells significantly reduced the expression of these genes, highlighting the role of Nfe2l1 in the regulation of PD-related pathways. Knockdown of Nfe2l1 also decreased Neat1, a long non-coding RNA associated with PD pathology, and downregulated the neuronal marker Map2, indicating impaired neuronal differentiation. Furthermore, Nfe2l1 knockdown increased ubiquitination under proteasome inhibition, emphasizing its role in protein degradation and neuronal homeostasis under stress. These findings highlight Nfe2l1 as a critical regulator in neuronal cells and reveal its potential role in maintaining proteostasis and involvement in neurodegenerative disease mechanisms, such as PD.

Parkinson Disease↗
PubMed2001

Well-differentiated endometrial adenocarcinomas and poorly differentiated mixed mullerian tumors have altered ER and PR isoform expression.

Both the estrogen receptor (ER) and the progesterone receptor (PR) have two subtypes: ER-alpha and beta, and PR-A and -B, respectively. These subtypes differ in function and expression, and recent reports have correlated changes in the normal proportions of these isoforms with neoplastic states. We investigated ER and PR isoform expression in normal pre- and post-menopausal endometrium, well-differentiated endometrial adenocarcinoma, and poorly differentiated malignant mixed mullerian tumors (MMMTs). Semi-quantitative RT-PCR and immunoblotting were used to measure receptor mRNA and protein expression. Estrogen receptor-alpha/beta mRNA ratios were significantly higher in postmenopausal (27.3) compared to premenopausal endometrium (4.9) mainly as a result of lower ER-beta expression in the former. Compared to age-matched postmenopausal controls, the ER-alpha/beta ratio was reduced in both grade I adenocarcinoma and MMMT specimens (3.3 and 6.8, respectively), due to a selective loss of ER-alpha. The relative abundance of PR-A and PR-B mRNA remained unchanged between all tissue subtypes. Total PR protein, however, was significantly reduced in MMMTs compared to all other groups. Thus, sex steroid receptor expression is significantly and differentially altered in well-differentiated and poorly-differentiated endometrial cancers. Both cancers exhibit decreased ER-alpha expression and the MMMTs also demonstrate a significant loss of PR protein.

Adenocarcinoma↗
PubMed1998

Intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus-like differentiation (CASTLE) exhibits CD5 immunoreactivity: new evidence for thymic differentiation.

AIMS: Cases of intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus-like differentiation (CASTLE) were examined for CD5 immunoreactivity, a feature of true thymic carcinoma, but not other thymic epithelial neoplasms or carcinomas of other sites. ITET/CASTLE, a rare, low-grade malignant neoplasm arising within the thyroid gland which resembles lymphoepithelioma-like and squamous cell carcinoma of the thymus, is postulated to arise from remnants of branchial pouch capable of thymic differentiation, but thymic differentiation in this neoplasm remains unproven. METHODS AND RESULTS: The largest published series of cases of ITET/CASTLE was examined for CD5 immunoreactivity using an anti-CD5 antibody reactive in fixed, paraffin-embedded tissue with microwave antigen retrieval. Neoplastic cells in all five cases of ITET/CASTLE studied were immunoreactive for CD5, including foci of tumour metastatic to lymph node and lung. In contrast, none of five cases of thyroid carcinoma with squamous differentiation was immunoreactive for CD5. A minority of cases of typical thyroid carcinomas showed some weak immunoreactivity for CD5. Other carcinomas of the head and neck were nonimmunoreactive for CD5. CONCLUSIONS: CD5 immunoreactivity in ITET/CASTLE is new evidence in support of thymic differentiation in this neoplasm.

Adult↗
PubMed2002

Epidermal differentiation: transgenic/knockout mouse models reveal genes involved in stem cell fate decisions and commitment to differentiation.

Epidermal development and differentiation are similar processes and therefore the study of one is likely to provide insight into the other. The signaling cascades required for epidermal differentiation are largely unknown. Recent evidence, however, has implicated two proteins, p63 and c-Myc, in different stages of epidermal development and differentiation. p63 was shown to be required for embryonic epidermal development. Mice lacking p63 do not develop stratified epithelia and appendages suggesting a role for p63 in the commitment to squamous epithelial lineages. Subsequent stem cell fate decisions are required to form the different structures of stratified epithelia including hair follicles, sebaceous glands, and epidermis. Several genes of the Wnt signaling pathway have been implicated in this process, including c-Myc, a downstream target of the Wnt pathway. Interestingly, targeted overexpression of c-Myc in the basal layer of the epidermis results in an increase in sebaceous gland size and number at the expense of hair follicles. This suggests that c-Myc promotes differentiation of epidermal stem cells into sebaceous glands. In this review, we discuss transgenic/knockout mouse models that have provided evidence linking c-Myc and p63 to different stages of epidermal development and differentiation.

Animals↗
PubMed1998

Differential expression of dystrophin isoforms and utrophin during dibutyryl-cAMP-induced morphological differentiation of rat brain astrocytes.

We have identified isoforms of dystrophin and utrophin, a dystrophin homologue, expressed in astrocytes and examined their expression patterns during dibutyryl-cAMP (dBcAMP)-induced morphological differentiation of astrocytes. Immunoblot and immunocytochemical analyses showed that full-length-type dystrophin (427 kDa), utrophin (395 kDa), and Dp71 (75 kDa), a small-type dystrophin isoform, were coexpressed in cultured nondifferentiated rat brain astrocytes and were found to be located in the cell membrane. During morphological differentiation of the astrocytes induced by 1 mM dBcAMP, the amount of Dp71 markedly increased, whereas that of dystrophin and utrophin decreased. Northern blot analyses revealed that dBcAMP regulates the mRNA levels of Dp71 and dystrophin but not that of utrophin. dBcAMP slightly increased the amount of the beta-dystroglycan responsible for anchoring dystrophin isoforms and utrophin to the cell membrane. Immunocytochemical analyses showed that most utrophin was observed in the cytoplasmic area during astrocyte differentiation, whereas Dp71 was found along the cell membrane of the differentiated astrocytes. These findings suggest that most of the dystrophin/utrophin-dystroglycan complex on cell membrane in cultured astrocytes was replaced by the Dp71-dystroglycan complex during morphological differentiation. The cell biological roles of Dp71 are discussed.

Animals↗
PubMed1985

Glucocorticoid regulation of adipocyte differentiation: hormonal triggering of the developmental program and induction of a differentiation-dependent gene.

We have analyzed the hormonal basis for the acceleration of differentiation by dexamethasone and insulin in the stable adipogenic cell line TA1. These cells, which were derived from 5-azacytidine-treated 10T1/2 mouse embryo fibroblasts, undergo differentiation in culture after reaching confluence. The ensuing morphological changes are accompanied by widespread alterations in the pattern of protein synthesis and the increased accumulation of specific mRNAs. Using cDNA clones corresponding to mRNAs that are induced during adipogenesis, we find that dexamethasone elicits the precocious accumulation of differentiation-specific gene products. This effect appears to be mediated by the glucocorticoid receptor, yet unlike standard steroid inductions, most of the RNAs reach the same maximal levels in the absence of dexamethasone. Glucocorticoids thus may increase the expression of a regulatory factor required for activating the entire set of differentiation-dependent genes. We also describe a gene whose transcription is not only activated during adipogenesis but is also specifically inducible by dexamethasone in the mature adipocyte. Moreover, the glucocorticoid responsiveness of this gene in differentiated cells appears to be dependent on its prior developmental activation.

Adipose Tissue↗
PubMed1987

Growth factor control of skeletal muscle differentiation: commitment to terminal differentiation occurs in G1 phase and is repressed by fibroblast growth factor.

Analysis of MM14 mouse myoblasts demonstrates that terminal differentiation is repressed by pure preparations of both acidic and basic fibroblast growth factor (FGF). Basic FGF is approximately 30-fold more potent than acidic FGF and it exhibits half maximal activity in clonal assays at 0.03 ng/ml (2 pM). FGF repression occurs only during the G1 phase of the cell cycle by a mechanism that appears to be independent of ongoing cell proliferation. When exponentially growing myoblasts are deprived of FGF, cells become postmitotic within 2-3 h, express muscle-specific proteins within 6-7 h, and commence fusion within 12-14 h. Although expression of these three terminal differentiation phenotypes occurs at different times, all are initiated by a single regulatory "commitment" event in G1. The entire population commits to terminal differentiation within 12.5 h of FGF removal as all cells complete the cell cycle and move into G1. Differentiation does not require a new round of DNA synthesis. Comparison of MM14 behavior with other myoblast types suggests a general model for skeletal muscle development in which specific growth factors serve the dual role of stimulating myoblast proliferation and directly repressing terminal differentiation.

Animals↗
PubMed1993

Commitment to differentiation and expression of early differentiation markers in murine keratinocytes in vitro are regulated independently of extracellular calcium concentrations.

In the epidermis, one of the earliest characterized events in keratinocyte differentiation is the coordinate induction of a pair of keratins specifically expressed in suprabasal cells, keratin 1 (K1) and keratin 10 (K10). Both in vivo and in vitro, extracellular calcium is necessary for several biochemical and structural changes during keratinocyte differentiation. However, it has been unclear if calcium serves as a differentiation signal in keratinocytes. In these studies, expression of suprabasal keratin mRNA and protein is used to test whether the initial differentiation of primary mouse keratinocytes in vitro is dependent on changes in the concentration of extracellular calcium. K1 mRNA was expressed at low levels in cultures of keratinocytes growing on plastic in 0.05 mM calcium but in attached cells was not further induced by increases in the concentration of extracellular calcium. Suspension of the keratinocytes into semi-solid medium induced a rapid and substantial increase in both expression of K1 mRNA and in the percentage of cells expressing suprabasal keratin proteins. The induction was unaffected by the concentration of calcium in the semi-solid medium and could not be enhanced by exposing attached cells to higher calcium before suspension. The induction of K1 mRNA could be inhibited by exposure of the keratinocytes to either EGF or fibronectin. These results suggest that commitment of mouse keratinocytes to terminal differentiation is independent of extracellular calcium and may be regulated primarily by extracellular factors other than calcium.

Animals↗
PubMed1978

Adaptive differentiation of murine lymphocytes. I. Both T and B lymphocytes differentiating in F1 transplanted to parental chimeras manifest preferential cooperative activity for partner lymphocytes derived from the same parental type corresponding to the chimeric host.

The concept of adaptive (selective) differentiation preducts that early differentiation of lymphocytes is conditioned by the environment in which such differentiation takes place. These processes appear to involve selection of lymphocytes according to their self-recognition between interacting lymphocytes is, at least in part, controlled by major histocompatibility complex-linked genes, then adaptive differentiation is also controlled by these genes. In these studies, we have tested the capacities of helper T lymphocytes and hapten-specific B lymphocytes primed in the environments of various combinations of bone marrow chimeras prepared between two parental strains (i.e. A/J and BALB/c) and their corresponding F1 hybrid (CAF1) to interact with primed B and T lymphocytes derived from conventional parent and F1 donors as well as all of the corresponding bone marrow chimera combinations. The results demonstrate clearly that (a) F1 transplanted to F1 chimeric lymphocytes display no restriction in terms of cooperative activity with all of the various partner cell combinations; (b) parent transplanted to F1 chimeric lymphocytes manifest effective cooperative activity only for partner cells from F) or parental donors corresponding to the haplotype of the original bone marrow donor, thereby behaving phenotypically just like conventional parental lymphocytes; and (c) F1 transplanted to parent chimeric lymphocytes display restricted haplotype preference in cooperating best with partner lymphocytes sharing the H-2 haplotype, either entirely or codomimantly, of the parental chimeric host. The implications of these findings for understanding certain controlling mechanisms for lymphocyte differentiation are discussed.

Animals↗