Control of Cell Growth and Differentiation during Early B-cell Development by Stromal Cell Molecules

Nishikawa, Shin‐Ichi; Hayashi, Seiji; Ogawa, Megumu; Kunisada, Takahiro; Nishikawa, Shin Ichi; Sudo, Tetsuo; Nakauchi, H; Suda, Taiji

doi:10.1101/sqb.1989.054.01.021

Cited by 5 publications

(5 citation statements)

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“…This type of receptor "cross-talk" is not unique to the IL-7R; aggregation of slg, CD40, and CD72 also phosphorylates CD19 (45,46). Previous observations suggest that pro-B cells may interact with stromal cells, possibly via CD19 binding with a stromal cell ligand, to enhance IL-7 production (3,5,69), and our data indicate that IL-7 could then interact with IL-7R on pro-B cells to initiate downregulation of TdT expression and the upregulation of CD19 expression. The RAG-1 and RAG-2 genes would continue to be expressed in the presence of IL-7 for as long as the CD19 ligation persists.…”

Section: Discussionmentioning

confidence: 94%

“…The in vitro demonstration of antagonistic effects of IL-7R and CD19 ligation on Ig gene recombinase activity raises the question of physiological relevance. Our results can be considered within the context of a stepwise differentiation model based on observations indicating that B cell precursors are initially dependent on stromal cell contact, then on stromal cells plus IL-7, and finally IL-7 alone as the precursor cells progressively differentiate to become immature surface Ig-expressing B cells (3,68). The idea of an intersection between the CD19-and IL-7R-signating pathways is favored by the observation of the phosphorylation of an unidentified 85-95-kD protein after IL-7R engagement (14,15); moreover, IL-7 may also induce phosphorylation of CD19 in precursor B cells (45).…”

Section: Discussionmentioning

confidence: 98%

“…he commitment of hemopoietic stem cell progeny to the B lineage and the progression of differentiation along this pathway are dependent on environmental cues provided by specialized cells in hemopoietic tissues (1)(2)(3). Stromal cells have been shown to mediate the development of B cell precursors through intercellular contact and via the action of secreted factors (4,5), including the stromal cell-derived cytokine IL-7 (6,7).…”

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confidence: 99%

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Immunoglobulin recombinase gene activity is modulated reciprocally by interleukin 7 and CD19 in B cell progenitors.

Billips

Núñez

Bertrand

et al. 1995

The Journal of Experimental Medicine

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SummaryBone marrow stromal cells promote B cell development involving recombinase gene-directed rearrangement of the immunoglobulin genes. We observed that the stromal cell-derived cytokine interleukin 7 (IL-7) enhances the expression of CD19 molecules on progenitor B-lineage cells in human bone marrow samples and downregulates the expression of terminal deoxynucleotidyl transferase (TdT) and the recombinase-activating genes RAG-1 and RAG-2. Initiation of the TdT downregulation on the first day of treatment, CD 19 upregulation during the second day, and RAG-1 and RAG-2 downmodulation during the third day implied a cascade of IL-7 effects. While CD19 ligation by divalent antibodies had no direct effect on TdT or RAG gene expression, CD19 cross-linkage complete blocked the IL-7 downregulation of RAG expression without affecting the earlier TdT response. These results suggest that signals generated through CD19 and the IL-7 receptor could modulate immunoglobulin gene rearrangement and repertoire diversification during the early stages of B cell differentiation.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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Immunoglobulin recombinase gene activity is modulated reciprocally by interleukin 7 and CD19 in B cell progenitors.

Billips

Núñez

Bertrand

et al. 1995

The Journal of Experimental Medicine

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“…First, existence of two distinct IB␣ degradation mechanisms strongly suggests that the in vivo signals responsible for the initial induction of NF-B in pre-B cells and the maintenance of nuclear NF-B in mature B cells may be different. The developmental microenvironment of bone marrow pre-B cells is characterized by the secretion of numerous cytokines and direct cell-cell contacts that are critical for their survival and differentiation (31,32). Some of these components likely provide signals necessary for proteasome-dependent induction of NF-B in pre-B cells.…”

Section: Discussionmentioning

confidence: 99%

A Switch in Distinct IκBα Degradation Mechanisms Mediates Constitutive NF-κB Activation in Mature B Cells

Fields

Seufzer

Oltz

et al. 2000

The Journal of Immunology

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Inducible activation of cytoplasmic NF-κB/Rel transcription factors occurs via proteasome-dependent degradation of an associated inhibitor, termed IκBα. Mature B lymphocytes constitutively express nuclear NF-κB, which is important for their long-term survival. The intrinsic mechanisms by which B cells constitutively activate NF-κB are unknown. In this paper we demonstrate that maintenance of NF-κB activity in primary B cells is mediated by a novel calcium-dependent, but proteasome-independent, mechanism. Moreover, we show that differentiation of conditionally transformed pre-B cells is accompanied by a switch from proteasome-dependent to proteasome-independent degradation of IκBα. Our findings indicate that IκBα degradation mechanisms are dynamic during B cell development, and ultimately establish constitutive NF-κB activity in mature B lymphocytes.

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“…Mouse fetal liver at days 11-13 contains precursors for both T and B lymphocytes as well as for myeloid cells (for review, see refs. [21][22][23].…”

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confidence: 99%

Establishment and characterization of lymphoid and myeloid mixed-cell populations from mouse late embryoid bodies, "embryonic-stem-cell fetuses".

Chen

Kosco

Staerz

1992

Proc. Natl. Acad. Sci. U.S.A.

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Mouse embryonic stem (ES) cells have the potential to differentiate into embryoid bodies in vitro and mimic normal embryonic development. The "ES fetus" is a specific development at a late stage seen under our culture conditions. We have established several mixed populations from ES fetuses by using combinations of retroviruses carrying different oncogenes (v-abl, v-raf, c-myc), interleukins 2 and 3, and Con A. Six groups ofmixed populations were characterized by immunophenotyping. For some groups, transfer of cells into sublethally irradiated mice resulted in the development of macrophages, mature T and B lymphocytes, and plasma cells of donor origin. Thus, these mixed populations may contain immortalized precursors of hematopoietic lineages. These mixed populations should be valuable for defining hematopoietic stem cells and their committed progenitors.

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Control of Cell Growth and Differentiation during Early B-cell Development by Stromal Cell Molecules

Cited by 5 publications

References 0 publications

Immunoglobulin recombinase gene activity is modulated reciprocally by interleukin 7 and CD19 in B cell progenitors.

Immunoglobulin recombinase gene activity is modulated reciprocally by interleukin 7 and CD19 in B cell progenitors.

A Switch in Distinct IκBα Degradation Mechanisms Mediates Constitutive NF-κB Activation in Mature B Cells

Establishment and characterization of lymphoid and myeloid mixed-cell populations from mouse late embryoid bodies, "embryonic-stem-cell fetuses".

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