Stromal Cell and Factor-Dependent B Lymphopoiesis in Culture

Kincade, Paul W.; Witte, Pamela L.; Landreth, Kenneth S.

doi:10.1007/978-3-642-71851-9_1

Cited by 15 publications

(2 citation statements)

References 78 publications

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“…In the bone marrow, developing B cells must remain in close contact with stromal cells to receive signals necessary for growth and maturation (26,41,42). Within the extravascular hematopoietic compartment, the earliest progenitor B cells (pro-B cells) are located within or near the endosteum (43).…”

Section: Discussionmentioning

confidence: 99%

Sustained Activation of Cell Adhesion Is a Differentially Regulated Process in B Lymphopoiesis

Glodek

Honczarenko

et al. 2003

The Journal of Experimental Medicine

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It is largely unknown how hematopoietic progenitors are positioned within specialized niches of the bone marrow microenvironment during development. Chemokines such as CXCL12, previously called stromal cell–derived factor 1, are known to activate cell integrins of circulating leukocytes resulting in transient adhesion before extravasation into tissues. However, this short-term effect does not explain the mechanism by which progenitor cells are retained for prolonged periods in the bone marrow. Here we show that in human bone marrow CXCL12 triggers a sustained adhesion response specifically in progenitor (pro- and pre-) B cells. This sustained adhesion diminishes during B cell maturation in the bone marrow and, strikingly, is absent in circulating mature B cells, which exhibit only transient CXCL12-induced adhesion. The duration of adhesion is tightly correlated with CXCL12-induced activation of focal adhesion kinase (FAK), a known molecule involved in integrin-mediated signaling. Sustained adhesion of progenitor B cells is associated with prolonged FAK activation, whereas transient adhesion in circulating B cells is associated with short-lived FAK activation. Moreover, sustained and transient adhesion responses are differentially affected by pharmacological inhibitors of protein kinase C and phosphatidylinositol 3-kinase. These results provide a developmental cell stage–specific mechanism by which chemokines orchestrate hematopoiesis through sustained rather than transient activation of adhesion and cell survival pathways.

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Section: Discussionmentioning

confidence: 99%

Sustained Activation of Cell Adhesion Is a Differentially Regulated Process in B Lymphopoiesis

Glodek

Honczarenko

et al. 2003

The Journal of Experimental Medicine

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“…Similar involvement of accessory cells is known to be important at different stages of normal B-cell development. For example, in vitro normal growth and differentiation of B lymphocytes involves associations between haemopoietic cells and the accessory cells of the bone marrow stromal cell layer (Whitlock & Witte, 1982); both factors produced by, and adherence to, stromal cells are vital for the maintenance of B lymphocytes (Kincade et al 1987). A number of different growth factors are involved (stem cell factor, IL7 and IL-6) (Funk & Witte, 1992;Takai et af, 1992;Roldan et af, 1992) and fibronetcin is important in contact with stroma (Roldan et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Accessory cells mediate hairy‐cell proliferation by mechanism (s) involving both adhesion and TNFα secretion

Till

Cawley

1994

Br J Haematol

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The mechanisms responsible for hairy-cell (HC) growth both in vitro and in vivo are still unclear. In a recent study we showed that monocytes/macrophages induce HC proliferation in vitro. The purpose of the present paper is to examine the specificity of this accessory cell effect and to establish the mechanism(s) involved. We demonstrate that the effect is not confined to monocytes/macrophages but is also potentially seen with a range of other cell types. However, at low accessory cell:HC ratios (< 1:20) only human umbilical vein endothelial cells (HUVEC) and macrophages induce HC proliferation. We suggest that these observations are of pathophysiological significance in relation to the close association frequently observed between HCs and endothelial cells/macrophages in the liver and spleen of patients with hairy-cell leukaemia (HCL). Regarding the mechanisms of the accessory cell effect, we show that both soluble factors and cell contact are important. A blocking anti-TNF alpha antibody abrogated the HC proliferation induced by HUVEC supernatant, indicating the involvement of this cytokine. Interaction of HCs with HUVEC via CD11b and 11c leucocyte integrins was shown to be important in the contact effect. Our demonstration of the involvement of both cytokines and cell contact in HC proliferation is in accord with what is already known about the control of B-cell growth and differentiation. More specifically, our results suggest that TNF alpha and interaction with endothelial cells/macrophages via leucocyte integrins are involved in the proliferation of late B-cells of the maturational stage represented by HCs.

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Stromal cell lines which support lymphocyte growth: characterization, sensitivity to radiation and responsiveness to growth factors

1988

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Stromal cells which grow as an adherent layer of Whitlock-Witte cultures are thought to be an essential component of the lymphohemopoietic microenvironment. Stromal cell lines from bone marrow (BM) and spleen have been obtained by treatment of cultures with 5-fluorouracil and selected for their lymphocyte support capacity by measuring the clonal growth of stromal cell-dependent lymphocyte lines in methyl cellulose. Established stromal cell lines differed significantly from stromal cells in primary Whitlock-Witte cultures with respect to expression of certain hemopoietic cell surface markers. For example, the Thy-1 and Mac-3 antigens were expressed by stromal cell lines obtained from BM and spleen, but not by stromal cells in primary cultures. Features common to all stromal cells include synthesis of actins, the neural adhesion molecule N-CAM, and a variety of collagens. Two types of common leukocyte antigens were not significantly expressed. The proliferation and total protein synthetic capacity of lymphocyte-supportive stromal cell lines was sensitive to ionizing radiation. After exposure of the cells to 200 rads, the incorporation of either [3H]thymidine or [3H]Leucine was reduced to less than 50% of control values, but the growth of lymphocytes was augmented in the presence of an irradiated stromal cell layer. The proliferation of stromal cell lines was also affected by exposure to a variety of growth factors. Addition of epidermal growth factor or endothelial cell growth factor augmented BM or spleen-derived stromal cell proliferation, while interferon-gamma had the opposite effect. In general, but not exclusively, lymphocyte growth was inhibited by factors which augmented the proliferation of stromal cells. Novel methods are described for isolating stromal cells and determining their capacity to support lymphocyte growth in vitro. Evidence is presented that this ability is not restricted to BM-derived stromal cells. The function of stromal cells was not dependent on their ability to proliferate, and this may be modulated by immunoregulatory and other growth factors.

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Stromal Cell and Factor-Dependent B Lymphopoiesis in Culture

Cited by 15 publications

References 78 publications

Sustained Activation of Cell Adhesion Is a Differentially Regulated Process in B Lymphopoiesis

Sustained Activation of Cell Adhesion Is a Differentially Regulated Process in B Lymphopoiesis

Accessory cells mediate hairy‐cell proliferation by mechanism (s) involving both adhesion and TNFα secretion

Stromal cell lines which support lymphocyte growth: characterization, sensitivity to radiation and responsiveness to growth factors

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