Recombinant Interleukin-7 Supports the Growth of Normal B Lymphocyte Precursors

1988 ◽  
pp. 16-18 ◽  
Author(s):  
G. Lee ◽  
A. E. Namen ◽  
S. Gillis ◽  
P. W. Kincade
Keyword(s):  
B Lymphocyte ◽  
Interleukin 7

scholarly journals Arrested B Lymphopoiesis and Persistence of Activated B Cells in Adult Interleukin 7−/− Mice

2001 ◽  
Vol 194 (8) ◽  
pp. 1141-1150 ◽  
Author(s):  
Thiago L. Carvalho ◽  
Tomaz Mota-Santos ◽  
Ana Cumano ◽  
Jocelyne Demengeot ◽  
Paulo Vieira
Keyword(s):  
T Cell ◽  
B Lymphocytes ◽  
Early Life ◽  
B Lymphocyte ◽  
Marginal Zone ◽  
Adult Life ◽  
Fold Increase ◽  
B Lymphopoiesis ◽  
Interleukin 7 ◽  
B1 Cells

Interleukin 7 is a crucial factor for the development of murine T and B lymphocytes. We now report that, in the absence of interleukin 7, B lymphocyte production takes place exclusively during fetal and perinatal life, ceasing after 7 wk of age. In peripheral organs, however, the pool of B lymphocytes is stable throughout adult life and consists only of cells that belong to the B1 and marginal zone (MZ) compartments. This is accompanied by a 50-fold increase in the frequency of immunoglobulin (Ig)M- and IgG-secreting cells, and the concentration of serum immunoglobulins is increased three- to fivefold. Both the MZ phenotype and the increase in serum IgM are T cell independent. These findings reveal a previously undescribed pathway of B lymphopoiesis that is active in early life and is interleukin 7 independent. This pathway generates B1 cells and a normal sized MZ B lymphocyte compartment.

scholarly journals Interleukin 7-dependent B lymphocyte precursor cells are ultrasensitive to apoptosis.

1994 ◽  
Vol 179 (6) ◽  
pp. 1789-1797 ◽  
Author(s):  
S D Griffiths ◽  
D T Goodhead ◽  
S J Marsden ◽  
E G Wright ◽  
S Krajewski ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Precursor Cells ◽  
Alpha Particles ◽  
Differential Sensitivity ◽  
X Rays ◽  
Interleukin 7 ◽  
Low Levels ◽  
B Cell Precursors

We have compared the sensitivity of clonogenic interleukin 7 (IL-7)-dependent murine B cell precursors with that of clonogenic mature B cells and myeloid precursors to alpha-particles from plutonium-238 and X radiation. All three populations are relatively sensitive, but B cell precursors are ultrasensitive. This differential sensitivity is also observed with corticosteroid, etoposide, and cisplatin, all apoptosis-inducing drugs used in the treatment of leukemia and other cancers. Further, we show that x-rays and drugs induce the bulk of the B cell precursor population to undergo rapid apoptosis, despite the continued presence of IL-7. B cell precursors were found to express very low levels of BCL-2 protein compared with mature splenic B cells and their resistance to x-rays and corticosteroid could be enhanced by expression of a BCL-2 transgene. These data have important implications for normal lymphopoiesis and for the behavior of leukemic lymphoid precursor cells.

Myeloid-biased hematopoietic stem cells have extensive self-renewal capacity but generate diminished lymphoid progeny with impaired IL-7 responsiveness

Blood ◽  
2004 ◽  
Vol 103 (11) ◽  
pp. 4111-4118 ◽  
Author(s):  
Christa E. Muller-Sieburg ◽  
Rebecca H. Cho ◽  
Lars Karlsson ◽  
Jing-F. Huang ◽  
Hans B. Sieburg
Keyword(s):  
B Lymphocyte ◽  
Gene Array ◽  
Hematopoietic Stem ◽  
Developmental Potential ◽  
Interleukin 7 ◽  
Gene Array Analysis ◽  
And Function ◽  
Transplantation Experiments ◽  
Serial Transplantation

Abstract The adult hematopoietic stem cell (HSC) compartment contains a substantial population of lineage-biased (Lin-bi) HSCs. Lin-bi HSCs generate cells of all hematopoietic lineages, albeit with skewed ratios of lymphoid to myeloid cells. The biased ratios are stable through serial transplantation, demonstrating that lineage bias is an inherent function of the HSCs. To define the mechanisms that cause lineage bias, the developmental potential of myeloid-biased (My-bi) HSCs was characterized. In serial transplantation experiments, My-bi HSCs contributed significantly longer to repopulation than other types of HSCs. The long lifespan indicates that My-bi HSCs are important for the persistence of HSC function throughout life. My-bi HSCs produce normal levels of myeloid precursors but reduced levels of precursors for the T- and B- lymphocyte lineages. Gene array analysis suggested that the lymphoid progeny of My-bi HSCs express lowered levels of interleukin-7 (IL-7) receptor. Indeed, the progeny derived from My-bi HSCs failed to respond to IL-7 in vitro. Thus, My-bi HSCs are programmed for diminished lymphopoiesis through a mechanism that involves a blunted response of its progeny to the central lymphokine IL-7. The data demonstrate that epigenetic regulation on the level of the HSCs can directly affect the number, composition, and function of the mature progeny.

Hyperexpression of interleukin-7 is not necessary or sufficient for transformation of a pre-B lymphoid cell line

1991 ◽  
Vol 11 (2) ◽  
pp. 854-863
Author(s):  
J C Young ◽  
M L Gishizky ◽  
O N Witte
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Protein Tyrosine Kinase ◽  
B Lymphocyte ◽  
Growth Stimulation ◽  
Malignant Phenotype ◽  
Interleukin 7 ◽  
B Lymphoid

Interleukin-7 (IL-7) is a potent stimulator of pre-B-lymphocyte proliferation. Pre-B cells transformed by a variety of oncogenes including those of the ABL protein tyrosine kinase family were screened for endogenous IL-7 mRNA expression by polymerase chain reaction and a sensitive bioassay for secreted IL-7. Some v-abl but none of the BCR/ABL, v-src, v-fms, v-myc, v-ras, or v-raf transformants analyzed contained elevated IL-7 transcripts. None of the cell lines secreted detectable bioactivity. We overexpressed IL-7 via a retroviral vector in an IL-7-dependent pre-B cell line to assess the potential for autocrine growth stimulation and malignant transformation. We achieved dramatic deregulation of IL-7 translational suppression by removing portions of the 5' flanking region. Levels of IL-7 expression much greater than those needed to establish factor-independent growth did not induce colony formation in agar by IL-7-expressing pre-B cell lines, and the majority of these lines were nontumorigenic in syngeneic mice. The same pre-B cell line transformed by v-abl displayed a highly malignant phenotype while containing dramatically lower IL-7 transcript levels. We conclude that endogenous IL-7 expression is not a necessary event in transformation of pre-B cells, nor is it sufficient to explain the malignant phenotype in v-abl-transformed cells. Up regulation of endogenous IL-7 expression in some transformed pre-B cells may be one of several synergistic events which can lead to malignant conversion.

scholarly journals Matrix Glycoprotein SC1/ECM2 Augments B Lymphopoiesis

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3404-3413 ◽  
Author(s):  
Kenji Oritani ◽  
Yuzuru Kanakura ◽  
Keisuke Aoyama ◽  
Takafumi Yokota ◽  
Neal G. Copeland ◽  
...  
Keyword(s):  
B Cells ◽  
Fusion Protein ◽  
B Lymphocyte ◽  
Transmembrane Protein ◽  
Critical Role ◽  
Preliminary Evidence ◽  
Dependent Manner ◽  
Terminal Portion ◽  
Amino Terminal ◽  
Interleukin 7

Abstract The extracellular matrix produced by stromal cells plays a critical role in lympho-hematopoiesis. It was recently discovered that matrix glycoprotein SC1/ECM2 is a component of that matrix and preliminary evidence suggested that it could contribute to the nurturing environment for B-lymphocyte precursors. A fusion protein prepared from the amino terminal portion of SC1/ECM2 and the constant region of human Ig preferentially bound to pre-B cells. Furthermore, the cloning efficiency of interleukin-7–dependent B-cell precursors was increased in a dose-dependent manner by addition of this fusion protein. We now report the complete cDNA sequence for murine SC1/ECM2 and its localization to the central region of chromosome 5. A fusion protein prepared from the full length of SC1/ECM2 and Ig was found to recognize pre-B cells in a divalent cation-dependent manner, and to augment mitogen-dependent proliferation of mature B cells, as well as the cloning of pre-B cells, but to have no influence on myeloid progenitor cells. Although SC1/ECM2 is normally a secreted protein, we show that it is also capable of augmenting lymphopoiesis when expressed as a transmembrane protein on fibroblasts. Although the C-terminal portion of SC1/ECM2 has sequence homology to osteonectin/SPARC, the unique N-terminal one fifth of the protein was sufficient to augment lymphocyte growth.

scholarly journals Molecular Basis for Hematopoietic/Mesenchymal Interaction during Initiation of Peyer's Patch Organogenesis

2001 ◽  
Vol 193 (5) ◽  
pp. 621-630 ◽  
Author(s):  
Kenya Honda ◽  
Hiroyasu Nakano ◽  
Hisahiro Yoshida ◽  
Satomi Nishikawa ◽  
Paul Rennert ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Molecular Basis ◽  
Cell Adhesion Molecule ◽  
B Lymphocyte ◽  
Lymphoid Cells ◽  
Intercellular Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Interleukin 7 ◽  
Β Receptor

Mice deficient in lymphotoxin β receptor (LTβR) or interleukin 7 receptor α (IL-7Rα) lack Peyer's patches (PPs). Deficiency in CXC chemokine receptor 5 (CXCR5) also severely affects the development of PPs. A molecular network involving these three signaling pathways has been implicated in PP organogenesis, but it remains unclear how they are connected during this process. We have shown that PP organogenesis is initiated at sites containing IL-7Rα+ lymphoid cells and vascular cell adhesion molecule (VCAM)-1/intercellular adhesion molecule (ICAM)-1 expressing nonlymphoid elements. Here we characterize these lymphoid and nonlymphoid components in terms of chemokine signals. The lymphoid population expresses CXCR5 and has a strong chemotactic response to B lymphocyte chemoattractant (BLC). Importantly, chemokines produced by VCAM-1+ICAM-1+ nonlymphoid cells mediate the recruitment of lymphoid cells. Furthermore, we show that these VCAM-1+ICAM-1+ cells are mesenchymal cells that are activated by lymphoid cells through the LTβR to express adhesion molecules and chemokines. Thus, promotion of PP development relies on mutual interaction between mesenchymal and lymphoid cells.

scholarly journals Hyperexpression of interleukin-7 is not necessary or sufficient for transformation of a pre-B lymphoid cell line.

1991 ◽  
Vol 11 (2) ◽  
pp. 854-863 ◽  
Author(s):  
J C Young ◽  
M L Gishizky ◽  
O N Witte
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Protein Tyrosine Kinase ◽  
B Lymphocyte ◽  
Growth Stimulation ◽  
Malignant Phenotype ◽  
Interleukin 7 ◽  
B Lymphoid

Interleukin-7 (IL-7) is a potent stimulator of pre-B-lymphocyte proliferation. Pre-B cells transformed by a variety of oncogenes including those of the ABL protein tyrosine kinase family were screened for endogenous IL-7 mRNA expression by polymerase chain reaction and a sensitive bioassay for secreted IL-7. Some v-abl but none of the BCR/ABL, v-src, v-fms, v-myc, v-ras, or v-raf transformants analyzed contained elevated IL-7 transcripts. None of the cell lines secreted detectable bioactivity. We overexpressed IL-7 via a retroviral vector in an IL-7-dependent pre-B cell line to assess the potential for autocrine growth stimulation and malignant transformation. We achieved dramatic deregulation of IL-7 translational suppression by removing portions of the 5' flanking region. Levels of IL-7 expression much greater than those needed to establish factor-independent growth did not induce colony formation in agar by IL-7-expressing pre-B cell lines, and the majority of these lines were nontumorigenic in syngeneic mice. The same pre-B cell line transformed by v-abl displayed a highly malignant phenotype while containing dramatically lower IL-7 transcript levels. We conclude that endogenous IL-7 expression is not a necessary event in transformation of pre-B cells, nor is it sufficient to explain the malignant phenotype in v-abl-transformed cells. Up regulation of endogenous IL-7 expression in some transformed pre-B cells may be one of several synergistic events which can lead to malignant conversion.

scholarly journals Inhibition of Interleukin 7 Receptor Signaling by Antigen Receptor Assembly

2000 ◽  
Vol 191 (4) ◽  
pp. 737-742 ◽  
Author(s):  
Fiona M. Smart ◽  
Ashok R. Venkitaraman
Keyword(s):  
Heavy Chain ◽  
B Lymphocyte ◽  
Antigen Receptor ◽  
Cytoplasmic Domain ◽  
Chain Gene ◽  
Inhibition Of Proliferation ◽  
Light Chain Gene ◽  
Murine Bone Marrow ◽  
Interleukin 7 ◽  
Receptor Assembly

After the productive rearrangement of immunoglobulin (Ig) heavy chain genes, precursor (pre-)B lymphocytes undergo a limited number of cell divisions in response to interleukin (IL)-7. Here, we present evidence that this phase of IL-7–dependent expansion is constrained by an inhibitory signal initiated by antigen receptor assembly. A line of pre-B cells from normal murine bone marrow that expresses a μ heavy chain with a D-proximal VH7183.2 region divides continuously in IL-7. IL-7 responsiveness ceases upon differentiation to the μ1, κ1 stage, despite continuing expression of the IL-7 receptor (IL-7R), suggesting that antigen receptor assembly inhibits IL-7 responsiveness. This is confirmed by introduction of a rearranged λ light chain gene, which inhibits proliferative signaling through the IL-7R. Inhibition is specific to the IL-7R, because it is overcome by replacement of the IL-7R cytoplasmic domain with corresponding sequences from the closely related IL-2Rβ chain. Alteration of a single tyrosine residue, Tyr410, in the IL-7R cytoplasmic domain to phenylalanine also prevents the inhibition of proliferation after antigen receptor assembly. Thus, the loss of IL-7 responsiveness after antigen receptor assembly may be mediated through the recruitment of an inhibitory molecule to this residue. Our findings identify a novel mechanism that limits cytokine-dependent proliferation during B lymphopoiesis. This mechanism may be essential for the proper regulation of peripheral B lymphocyte numbers.

Sign in / Sign up

Export Citation Format

Share Document