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At least 19 recordsLinked to original sources
PubMed2005

Chronic zinc deficiency in mice disrupted T cell lymphopoiesis and erythropoiesis while B cell lymphopoiesis and myelopoiesis were maintained.

OBJECTIVE: The purpose of this study was to determine the impact of chronic zinc deficiency (ChrZD) on T and B cell lymphopoiesis, myelopoiesis and erythropoiesis in mice. METHODS: Young adult mice were fed a zinc adequate (ZA) or ChrZD synthetic diet for 34, 45, and 50 days. The cellular composition of the thymus and marrow were determined to assess the impact of ChrZD on lymphopoietic and hematopoietic processes using flow cytometry. Body weights, serum zinc and corticosterone (Cs) were monitored. RESULTS: For ChrZD mice growth was reduced 10% and serum zinc declined 15% by d 34 compared to ZA mice. By d 50 a 25% decrease in growth and 70% depression in serum zinc was noted though there was never any significant reduction in diet intake. Corticosterone rose 2.5 fold by d 34 and remained elevated in ChrZD mice indicating induction of the stress axis. At d 34 the thymus of ChrZD mice was normal but by d 50 there was a 50% cell loss and a 10% reduction in the proportion of Pre-T cells. Most importantly there was a 60% increase in Pre-T cells undergoing apoptosis in ChrZD mice. Pro-T, T helper, and T cytolytic populations were more resistant to ChrZD. Bone marrow cellularity and granulocyte, monocyte, and lymphocyte compartments remained unchanged in ChrZD mice. However, the erythroid compartment was reduced by 35% at d 50. CONCLUSIONS: The thymus was the most sensitive primary tissue to ChrZD. By d 50 it had atrophied by 36% with significant loss of Pre-T cells via apoptosis such that T-cell lymphopoiesis was disrupted. Significant reductions were also noted in the erythropoietic population by d 50. Conversely the marrow maintained myelopoiesis and B cell lymphopoiesis for the 50 d period indicating greater ability to survive a chronic zinc deficiency and exposure to Cs. The anemia and T cell lymphopenia associated with ChrZD in both rodents and humans may result from a greater sensitivity of their precursor cells to zinc deficiency and elevated Cs.

Animals↗
PubMed1997

Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function: similarity to estrogen deficiency.

Estrogen deficiency caused by ovariectomy (OVX) results in a marked bone loss due to stimulated bone resorption by osteoclasts. During our investigations of the pathogenesis of bone loss in estrogen deficiency, we found that OVX selectively stimulates B-lymphopoiesis which results in marked accumulation of B220-positive pre-B cells in mouse bone marrow. To examine the possible correlation between stimulated B-lymphopoiesis and bone loss, 8-week-old female mice were treated with interleukin (IL) 7, which stimulates B-lymphopoiesis in bone marrow. We also examined bone mass in IL-7 receptor-knockout mice that exhibit marked suppression of B-lymphopoiesis in the bone marrow. The increased B-lymphopoiesis induced by IL-7 administration resulted in marked bone loss by stimulation of osteoclastic bone resorption in mice with intact ovarian function. The changes in both B-lymphopoiesis and bone mass in IL-7-treated female mice were similar to those in age-matched OVX mice. In contrast, the trabecular bone volume of the femur was greatly increased in both female and male IL-7 receptor-knockout mice when compared with the respective wild-type and heterozygous littermates. These results show that the perturbation of B-lymphopoiesis in the bone marrow is closely linked to the change in bone mass. We propose here that the increased B-lymphopoiesis due to estrogen deficiency is involved in the mechanism of stimulated bone resorption.

Animals↗
PubMed2007

Inflammatory biomarker, neopterin, suppresses B lymphopoiesis for possible facilitation of granulocyte responses, which is severely altered in age-related stromal-cell-impaired mice, SCI/SAM.

Neopterin is produced by monocytes and is a useful biomarker of inflammatory activation. We found that neopterin enhanced in vivo and in vitro granulopoiesis triggered by the stromal-cell production of cytokines in mice. The effects of neopterin on B lymphopoiesis during the enhancement of granulopoiesis were determined using the mouse model of senescent stromal-cell impairment (SCI), a subline of senescence-accelerated mice (SAM). In non-SCI mice (a less senescent stage of SCI mice), treatment with neopterin decreased the number of colonies, on a semisolid medium, of colony-forming units of pre-B-cell progenitors (CFU-preB) from unfractionated bone marrow (BM) cells, but not that from a population rich in pro-B and pre-B cells without stromal cells. Neopterin upregulated the expression of genes for the negative regulators of B lymphopoiesis such as tumor necrosis factor-alpha (TNF-alpha ), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta) in cultured stromal cells, implying that neopterin suppressed the CFU-preB colony formation by inducing negative regulators from stromal cells. The intraperitoneal injection of neopterin into non-SCI mice resulted in a marked decrease in the number of femoral CFU-preB within 1 day, along with increases in TNF-alpha and IL-6 expression levels. However, in SCI mice, in vivo and in vitro responses to B lymphopoiesis and the upregulation of cytokines after neopterin treatment were less marked than those in non-SCI mice. These results suggest that neopterin predominantly suppressed lymphopoiesis by inducing the production of negative regulators of B lymphopoiesis by stromal cells, resulting in the selective suppression of in vivo B lymphopoiesis. These results also suggest that neopterin facilitated granulopoiesis in BM by suppressing B lymphopoiesis, thereby contributing to the potentiation of the inflammatory process; interestingly, such neopterin function became impaired during senescence because of attenuated stromal-cell function, resulting in the downmodulation of the host-defense mechanism in the aged.

Aging↗
PubMed2000

Comparative effects of estrogen and raloxifene on B lymphopoiesis and bone loss induced by sex steroid deficiency in mice.

Estrogen deficiency caused by ovariectomy (OVX) results in a marked bone loss because of stimulated bone resorption. We have reported that OVX selectively stimulates B lymphopoiesis in mouse bone marrow, which is somehow related to bone resorption. Estrogen prevents both the increased B lymphopoiesis and the bone resorption caused by estrogen deficiency. Raloxifene also has a potent estrogenic activity for bone with minimal estrogenic activity for the uterus. To examine the effects of raloxifene on B lymphopoiesis and bone resorption, OVX mice were given either estrogen or raloxifene subcutaneously for 2-4 weeks using a miniosmotic pump. Reduced uterine weight in OVX mice was restored completely by 17beta-estradiol (E2). Some 300-fold higher doses of raloxifene increased uterine weight of OVX mice, but only slightly. The number of B220- positive pre-B cells was increased markedly in bone marrow after OVX. The increased B lymphopoiesis was prevented not only by E2 but by raloxifene. In OVX mice, the trabecular bone volume (BV) of the femoral distal metaphysis was reduced markedly, when measured by microcomputed tomography (microCT) scanning and dual-energy X-ray absorptiometry. Both E2 and raloxifene similarly restored it. Like estrogen deficiency, androgen deficiency induced by orchidectomy (ORX) also resulted in a marked bone loss and increased B lymphopoiesis. Both E2 and raloxifene prevented the changes in ORX mice. These results indicate that both estrogen deficiency and androgen deficiency similarly stimulate B lymphopoiesis in mouse bone marrow, which accompany bone loss. Raloxifene exhibits estrogenic actions in bone and bone marrow to prevent bone loss and regulate B lymphopoiesis without inducing estrogenic action in the uterus.

Androgens↗
PubMed2000

Intramedullary and extramedullary B lymphopoiesis in osteopetrotic mice.

Adult bone marrow is a major site for hematopoiesis, and reduction of the bone marrow cavity induces hematopoiesis in extramarrow tissues. To investigate the rudimentary intramarrow and the compensatory extramarrow hematopoiesis, particularly B lymphopoiesis, we used 3 osteopetrotic mouse strains [op/op, mi/mi, and Fos (-/-)], which are severely deficient in functional osteoclasts and therefore form inadequate bone marrow cavities. We found that bone marrow in these osteopetrotic mice supports myelopoiesis but not B lymphopoiesis, although cells that have the potential to differentiate into B lineage cells are present in the bone marrow. Although B lymphopoiesis normally occurs both in the spleen and liver of newborn mice, compensatory B lymphopoiesis in adult op/op and mi/mi mice is observed only in the liver, while myelopoiesis is enhanced in both organs. Interestingly, mice lacking the Fos proto-oncogene exhibit B lymphopoiesis in the spleen as well as liver. The amounts of expression of steel factor, Flt3/Flk-2 ligand, and interleukin-7 in the bone marrow, spleen, or liver were not significantly affected in these osteopetrotic mutants. These findings suggest that the volume of the bone marrow cavity regulates B lymphopoiesis without affecting the production of certain hematopoietic growth factors. The splenic microenvironments that support both myelopoiesis and B lymphopoiesis in the neonatal stage are lost in adults and are not reactivated even in the osteopetrotic adults unless the Fos gene is disrupted.

Aging↗
PubMed2006

Wnt expression and canonical Wnt signaling in human bone marrow B lymphopoiesis.

BACKGROUND: The early B lymphopoiesis in mammals is regulated through close interactions with stromal cells and components of the intracellular matrix in the bone marrow (BM) microenvironment. Although B lymphopoiesis has been studied for decades, the factors that are implicated in this process, both autocrine and paracrine, are inadequately explored. Wnt signaling is known to be involved in embryonic development and growth regulation of tissues and cancer. Wnt molecules are produced in the BM, and we here ask whether canonical Wnt signaling has a role in regulating human BM B lymphopoiesis. RESULTS: Examination of the mRNA expression pattern of Wnt ligands, Fzd receptors and Wnt antagonists revealed that BM B progenitor cells and stromal cells express a set of ligands and receptors available for induction of Wnt signaling as well as antagonists for fine tuning of this signaling. Furthermore, different B progenitor maturation stages showed differential expression of Wnt receptors and co-receptors, beta-catenin, plakoglobin, LEF-1 and TCF-4 mRNAs, suggesting canonical Wnt signaling as a regulator of early B lymphopoiesis. Exogenous Wnt3A induced stabilization and nuclear accumulation of beta-catenin in primary lineage restricted B progenitor cells. Also, Wnt3A inhibited B lymphopoiesis of CD133+CD10- hematopoietic progenitor cells and CD10+ B progenitor cells in coculture assays using a supportive layer of stromal cells. This effect was blocked by the Wnt antagonists sFRP1 or Dkk1. Examination of early events in the coculture showed that Wnt3A inhibits cell division of B progenitor cells. CONCLUSION: These results indicate that canonical Wnt signaling is involved in human BM B lymphopoiesis where it acts as a negative regulator of cell proliferation in a direct or stroma dependent manner.

Animals↗
PubMed1999

Stromal cell-derived factor 1 (SDF-1) and antenatal human B cell lymphopoiesis: expression of SDF-1 by mesothelial cells and biliary ductal plate epithelial cells.

The chemokine stromal cell-derived factor 1 (SDF-1) stimulates the growth of pre-B cells in vitro, and mice with a disrupted SDF-1 gene have abnormal fetal liver B cell lymphopoiesis. The origin of SDF-1 production has not been determined yet. Using an anti-SDF-1 mAb, we performed immunohistochemical studies in four human embryos and five fetuses to define which cells express the SDF-1 protein at sites of antenatal B cell lymphopoiesis. All mesothelial cells contained SDF-1 at all stages of development, including in the intraembryonic splanchnopleuric mesoderm early into gestation. In fetal lungs and kidneys, SDF-1 was expressed by epithelial cells, and a few B lymphoid precursors, expressing V pre-B chains, were also detected. In the fetal liver, in addition to mesothelial cells, biliary epithelial cells were the only cells to contain SDF-1. Pre-B cells expressing V chains were abundant and exclusively located around the edge of portal spaces, in close contact with biliary ductal plate epithelial cells. They did not colocalize with biliary collecting ducts. Biliary ductal plate epithelial cells and liver B cell lymphopoiesis display a parallel development and disappearance during fetal life. These results indicate that early B cell lymphopoiesis in the splanchnopleura may be triggered by mesothelial cells producing SDF-1. Later into gestation, biliary ductal plate epithelial cells may support B cell lymphopoiesis, thus playing a role similar to that of epithelial cells in the avian bursa of Fabricius, and of thymic epithelial cells for T cell lymphopoiesis.

Amino Acid Sequence↗
PubMed1968

Incorporation of sulfate by the mouse thymus: its relation to secretion by medullary epithelial cells and to thymic lymphopoiesis.

The thymus was examined in suckling mice during normal development and the involution and regeneration produced by injection of cortisol, in experiments designed to test the hypothesis that medullary epithelial cells secrete a ymphopoietic hormone responsible for controlling the magnitude of thymic lymphopoiesis. Cellular events were observed by light and electron microscopy. Lymphopoiesis was assessed, after injection of thymidine-(3)H, by counting the proportion of lymphocytes labeled in radioautographs of thymus. Cortical lymphopoiesis was distributed heterogeneously, being concentrated in the subcapsular region, but medullary lymphopoiesis was statistically homogeneous in distribution and similar in magnitude to the average level of cortical lymphopoiesis in suckling mice. Therefore counts of the labeling index in the medulla were used to estimate the size of the proliferating population of lymphocytes. Epithelial secretory activity was estimated by measuring the incorporation of (36)sulfate by the thymus, using gel filtration chromatography to isolate soluble macromolecular (35)sulfate-presumed on radioautographic evidence to represent the mucoid epithelial secretory product. Incorporated (35)sulfate accumulated rapidly for 4 hr, reached a peak at 12 hr, and had fallen to half that level by 24 hr after a single injection-as would be expected of a secretory product. During normal postnatal development the size of the proliferating population of lymphocytes and the magnitude of (35)sulfate incorporation increased in parallel. During acute involution induced by cortisol both parameters diminished greatly but rose to high levels during subsequent regeneration. Accordingly, lymphopoiesis and sulfate incorporation -as defined and measured in these experiments-correlated linearly over a wide range of variation, providing circumstantial evidence to support the hypothesis that medullary epithelial cells secrete a sulfated mucoid lymphopoietic hormone. This conclusion is discussed in terms of the roles of thymus and adrenal cortex in development of the lymphoid system and maturation of immunological competence.

Adrenal Glands↗
PubMed2003

Oestrogen receptor specificity in oestradiol-mediated effects on B lymphopoiesis and immunoglobulin production in male mice.

Oestrogen treatment down-regulates B lymphopoiesis in the bone marrow of mice. Meanwhile it up-regulates immunoglobulin production. To understand better the oestrogen action on bone marrow male mice lacking oestrogen receptor alpha (ERalpha; ERKO mice), lacking ERbeta (BERKO mice), lacking both receptors (DERKO mice) or wild-type (wt) littermates were castrated and treated for 2.5 weeks with 30 microg/kg 17beta-oestradiol (E2) or vehicle oil as controls. The B lymphopoiesis in the bone marrow was examined by flow cytometry and mature B-cell function was studied using an ELISPOT assay enumerating the B cells in bone marrow and spleen that were actively producing immunoglobulins. In wt mice the frequency of B-lymphopoietic (B220+) cells in the bone marrow decreased from 15% to 5% upon E2 treatment. In ERKO and BERKO mice significant reduction was seen but not of the same magnitude. In DERKO mice no reduction of B lymphopoiesis was seen. In addition, our results show that E2 mediated reduction of different steps in B lymphopoiesis require only ERalpha or both receptors. In wt and BERKO mice E2 treatment resulted in significantly increased levels of B cells actively producing immunoglobulin, while in ERKO and DERKO mice no such change was seen. Similar results were found in both bone marrow and spleen. In conclusion our results clearly show that both ERalpha and ERbeta are required for complete down-regulation of B lymphopoiesis while only ERalpha is needed to up-regulate immunoglobulin production in both bone marrow and spleen.

Animals↗
PubMed1992

Mechanisms by which benzo[a]pyrene, an environmental carcinogen, suppresses B cell lymphopoiesis.

The capacity for polycyclic aromatic hydrocarbons (PAH) to suppress immune cell function has been well documented. Nevertheless, mechanisms responsible for PAH immunosuppression and potential effects of PAH on lymphocyte development (lymphopoeisis) remain poorly defined. Murine bone marrow cultures were used in the present studies to determine if and by what mechanism(s) benzo[a]pyrene (B[a]P), a prototypic and highly carcinogenic PAH, suppresses B cell lymphopoiesis. Emphasis was placed on similarities between the processes leading to transformation and immunosuppression and on a possible role for programmed cell death (apoptosis) in B[a]P lymphotoxicity. Data presented herein indicate that: (1) B[a]P suppresses B cell lymphopoiesis in bone marrow cultures at extremely low concentrations (10(-8) M); (2) benzo[e]pyrene, the relatively noncarcinogenic congener of B[a]P, is approximately 1000 times less potent than B[a]P in suppressing B cell lymphopoiesis; (3) bone marrow cells from PAH-resistant DBA/2 mice are less sensitive to B[a]P than cells from C57BL/6 mice; (4) B[a]P induces preB cell apoptosis; and (5) alpha-naphthaflavone, an inhibitor of Ah-receptor dependent, P450 isoenzyme activity, blocks B[a]P-mediated preB cell apoptosis and inhibits B[a]P-dependent suppression of lymphopoiesis. The results support the hypothesis that B[a]P suppression of B cell lymphopoiesis is mediated at least in part by the induction of programmed cell death and that the Ah receptor and/or P450 isoenzymes are involved in this process. The results suggest the potential for PAH to affect development of the B lymphocyte repertoire.

Animals↗
PubMed2000

Intestinal inflammation observed in IL-2R/IL-2 mutant mice is associated with impaired intestinal T lymphopoiesis.

BACKGROUND & AIMS: Although interleukin (IL)-2(-/-) and IL-2Ralpha(-/-) mice develop inflammatory bowel disease, IL-2Rbeta(-/-) animals are apparently free of gut pathology. Intraintestinal T lymphopoiesis is reported to be impaired in IL-2Rbeta(-/-) mice; we have determined whether this characteristic correlated with the apparent resistance of this mutant strain to intestinal inflammation. This led us to reassess intraintestinal T lymphopoiesis in these 3 mutant strains. METHODS: Intestinal histology and intraintestinal T lymphopoiesis were analyzed in unmanipulated mutant mice and in athymic and euthymic radiation chimeras reconstituted with bone marrow derived from IL-2(-/-), IL-2Ralpha(-/-), and IL-2Rbeta(-/-) donors. RESULTS: Intraintestinal T lymphopoiesis was ablated in the 3 mutant strains and was associated with cryptopatch abnormalities. The intestinal mucosa of mice reconstituted with lymphocytes from IL-2Rbeta(-/-) mice exhibited lesions of both the small and large bowel similar to those observed in the early stages of human gluten enteropathy and acute ulcerative colitis, respectively. Analysis of euthymic and athymic bone marrow radiation chimeras indicated that T cells located in the intestinal mucosa of unmanipulated IL-2(-/-), IL-2Ralpha(-/-), and IL-2Rbeta(-/-) mice are of thymic origin. CONCLUSIONS: Null mutations at IL-2/IL-2Ralpha and beta loci differentially affect intraintestinal and intrathymic T lymphopoiesis. These conditions are associated with lesions of intestinal inflammation that are mediated by thymus-derived T cells.

Animals↗
PubMed2001

B lymphopoiesis is upregulated after orchiectomy and is correlated with estradiol but not testosterone serum levels in aged male rats.

Previous studies have shown that B lymphopoiesis is augmented after androgen withdrawal in male mice. As an analogy to the skeletal system, some effects of androgens on the proliferation of B cells may be mediated via aromatization into estrogens in vivo. The aim of the present study was to assess the effects of androgen withdrawal on B lymphopoiesis in bone marrow of aged male rats sequentially over a period of 9 months, and to correlate the flow-cytometric findings with changes in systemic levels of sex steroids. We first showed that androgen withdrawal is associated with enhanced B lymphopoiesis in bone marrow of 4-month-old male orchiectomized (ORX) rats, and that the changes in the bone marrow B cell compartment in ORX animals can be reversed by testosterone supplementation. In a subsequent, sequential experiment, we found that orchiectomy induced a sustained rise in Thy 1.1+/CD45R+ bone marrow cells committed for the B cell lineage that lasted for several months in 13-month-old aged rats. In a stepwise model of multiple regression analysis using estradiol, free and total testosterone as independent variables, estradiol was the strongest predictor of the percentage of B precursor cells in bone marrow in aged SHAM and ORX rats. Free and total testosterone did not correlate with B lymphopoiesis in aged SHAM rats. The current experiment has clearly shown that androgen withdrawal upregulates the number of B lineage cells over several months in rat bone marrow. Furthermore, our results provide evidence that estradiol may play an important role as a physiological suppressor of B lymphopoiesis in aged male rats.

Aging↗
PubMed1991

An experimental and mathematical analysis of lymphopoiesis dynamics under continuous irradiation.

A mathematical model describing the dynamics of lymphopoiesis in mammals continuously exposed to ionizing radiation has been developed. It is based on the theory of chalone regulation of hematopoiesis. The model comprises a system of nine differential equations. Results from the model were compared with our experimental data for bone marrow and blood lymphocytes of rats continuously exposed to gamma radiation in a wide range of dose rates. The model reproduces the lymphopoiesis dynamics that we observed in our experiment, in particular, the radiation hormesis at low dose rates, the reduction of lymphopoiesis at intermediate dose rates, and extinction of lymphopoiesis at high dose rates of continuous radiation. The possible explanation of the hormesis is suggested by the framework of the model. The model can be used for predicting the lymphopoiesis dynamics in mammals under continuous irradiation.

Animals↗
PubMed2000

Impairment of lymphopoiesis and myelopoiesis in mice reconstituted with bone marrow-hematopoietic progenitor cells expressing SDF-1-intrakine.

Both SDF-1 and CXCR4 disruption are lethal to mice at the embryonic stage and cause abnormalities in B lymphopoiesis, myelopoiesis, cardiogenesis, vasculogenesis, and cerebellar development. To investigate the role of SDF-1 and CXCR4 in hematopoiesis during the adult stage, mice reconstituted with bone marrow-derived hematopoietic progenitor cells transduced with either the SDF-1 or a genetically modified SDF-1-intrakine gene using a retroviral expression vector were analyzed. Flow cytometric (FCM) analysis showed a dramatic reduction of CXCR4 expression on the cells of intrakine-transduced mice, whereas CCR7 and CCR1 expression was unchanged or marginally decreased on splenocytes. Migration of splenocytes and bone marrow cells to SDF-1 was markedly suppressed in intrakine-transduced mice. FCM analysis of bone marrow cells of intrakine-transduced mice exhibited decreased numbers of pro-B (B220(+) CD43(+)), pre-B (B220(+) CD43(-)), and immature B (B220(+) IgM(+)) cells and a decreased number of granulocytes/myeloid (Gr1(+) CD11b(+)) cells. Impaired B lymphopoiesis and myelopoiesis in intrakine-transduced mice were confirmed by an in vitro colony-forming assay of bone marrow cells. In contrast, B lymphopoiesis and myelopoiesis were enhanced in SDF-1-transduced mice. Interestingly, T-cell maturation in the thymus was impaired both in intrakine- and SDF-1-transduced mice, suggesting that SDF-1 and CXCR4 play an important role in T lymphopoiesis as well as in B lymphopoiesis and myelopoiesis in adults. These results demonstrate an essential role of CXCR4 and its ligand SDF-1 in adult hematopoiesis, and they indicate the intrakine method as a powerful tool for functional analysis of chemokines/chemokine receptors in vivo and as a potential therapeutic approach for acquired immunodeficiency syndrome.

Animals↗
PubMed1988

Interleukin-1 inhibition of B lymphopoiesis is reversible.

Interleukin-1 (IL-1) has multiple effects on the hematopoietic system. The present data demonstrate that IL-1 and/or products induced by it reversibly suppress B-cell differentiation. Upon the addition of 50 U/mL (2.4 ng/mL) of recombinant IL-1 alpha (rIL-1 alpha) to lymphoid long-term bone marrow cultures at their initiation, very few B lymphocytes could be detected, and the majority of cells present were myeloid. This inhibition of B lymphopoiesis did not appear to be due to effects on proliferation of mature B cells because IL-1 did not affect the proliferative response of B cells to form B-cell colonies (CFU-B). The actions of the monokine were further examined by using myeloid and lymphoid long-term bone marrow culture systems. The transfer of myeloid long-term bone marrow cultures to lymphoid conditions usually results in the cessation of myelopoiesis and initiation of B lymphopoiesis. Exposure of early B-cell precursors present under the myeloid conditions to 50 U/mL of RIL-1 did not affect their subsequent differentiation into B cells upon transfer of the cultures to lymphoid conditions. However, myelopoiesis was sustained, and B lymphopoiesis did not initiate if 50 U/mL of rIL-1 was added to myeloid bone marrow cultures at the time of their transfer to the lymphoid conditions and during biweekly feedings thereafter. Upon removal of IL-1, myelopoiesis ceased, and B lymphopoiesis initiated. Thus, the effects of IL-1 on inhibition of B lymphopoiesis are reversible.

Animals↗
PubMed2003

Active form of Notch members can enforce T lymphopoiesis on lymphoid progenitors in the monolayer culture specific for B cell development.

The in vitro induction of T lymphopoiesis needs the precise stereoscopic structure of thymus tissues as seen in fetal thymus organ culture. In this study, we demonstrated for the first time that the introduction of the intracellular region of Notch1 can induce T cells expressing TCR without any thymic environment. In the coculture on the monolayer of OP-9, which was originally known to support B cell specific development, hemopoietic progenitors developed into Thy-1(+)CD25(+) T lineage cells if the progenitor cells were infected with the retrovirus containing Notch1 intracellular domains. The Thy-1(+) cells progressed to a further developmental stage, CD4 and CD8 double-positive cells expressing TCR on the cell surface, if they were further cultured on OP-9 or in the thymus. However, T cell induction by intracellular Notch1 failed unless both OP-9 and IL-7 were present. It is notable that Notch2 and Notch3 showed an effect on T lymphopoiesis similar to that of Notch1. These results indicate that in vitro T lymphopoiesis is inducible by signaling via Notch family members in a lineage-specific manner but shares other stroma-derived factors including IL-7 with B lymphopoiesis.

Animals↗
PubMed2003

The onecut transcription factor hepatocyte nuclear factor-6 controls B lymphopoiesis in fetal liver.

Mouse genetic models have helped to identify transcription factors that are expressed by hemopoietic cells and control their differentiation into lymphoid cells. However, little is known on transcription factors that are involved in this process, but are expressed in nonhemopoietic cells of the microenvironment. We show in this study that inactivation of the gene coding for hepatocyte nuclear factor-6 (HNF-6) in mice led to B lymphopenia in the bone marrow and spleen. This phenotype disappeared shortly after birth when fetal B lymphopoiesis is no longer active, pointing to a defect in fetal liver. Indeed, the number of B cells was decreased in this organ as well. An analysis of B cell developmental markers in fetal liver cells showed that B lymphopoiesis was impaired just beyond the pre-pro B cell stage. Hemopoietic cells from hnf6(-/-) fetal liver could reconstitute the lymphoid system when injected into scid mice. Because parenchymal cells, but not hemopoietic cells, expressed hnf6 in normal liver, we concluded that HNF-6 controls B lymphopoiesis in fetal liver and that HNF-6 exerts this control indirectly by acting in parenchymal cells. The involvement, in the B cell defect of hnf6(-/-) fetuses, of genes known to exert such an indirect control was ruled out by expression analysis, including microarrays, and by in vivo rescue experiments. This work identifies HNF-6 as the first noncell-intrinsic transcription factor known to control B lymphopoiesis specifically in fetal liver.

Animals↗