Monoclonal antibodies that block adhesion of B cell progenitors to bone marrow stroma <i>in vitro</i> prevent B cell differentiation <i>in vivo</i>

Imhof, Beat A.; Schlienger, Claude; Handloser, Klaus; Hesse, B; Slanicka, M.; Gisler, Roland H.

doi:10.1002/eji.1830210911

Cited by 8 publications

(1 citation statement)

References 46 publications

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“…LFA-1 is also expressed by B cells promoting cell adhesion, thereby facilitating immunological synapse formation and B cell activation (55). mAbs that block adhesion of B cell progenitors to BM stroma cells in vitro prevent B cell differentiation in vivo (56). In line with this, we observed that ICAM-1-Fc consistently increased the absolute amount of B cells, although it was dispensable for early B cell development.…”

Section: Discussionsupporting

confidence: 61%

A Feeder-Free Differentiation System Identifies Autonomously Proliferating B Cell Precursors in Human Bone Marrow

Kraus

Kaiser

Aumann

et al. 2014

The Journal of Immunology

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The peripheral B cell compartment is maintained by homeostatic proliferation and through replenishment by bone marrow precursors. Because hematopoietic stem cells cycle at a slow rate, replenishment must involve replication of precursor B cells. To study proliferation of early human B cell progenitors, we established a feeder cell–free in vitro system allowing the development of B cells from CD34+ hematopoietic stem cells up to the stage of immature IgM+ B cells. We found that pro-B and pre-B cells generated in vitro can proliferate autonomously and persist up to 7 wk in culture in the absence of signals induced by exogenously added cytokines. Nevertheless, addition of IL-7 enhanced pre-B cell expansion and inhibited maturation into IgM+ B cells. The B cell precursor subsets replicating in vitro were highly similar to the bone marrow B cell precursors cycling in vivo. The autonomous proliferation of B cell precursor subsets in vitro and their long-term persistence implies that proliferation during pro-B and pre-B cell stages plays an important role in the homeostasis of the peripheral B cell compartment. Our in vitro culture can be used to study defects in B cell development or in reconstitution of the B cell pool after depletion and chemotherapy.

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Section: Discussionsupporting

confidence: 61%

A Feeder-Free Differentiation System Identifies Autonomously Proliferating B Cell Precursors in Human Bone Marrow

Kraus

Kaiser

Aumann

et al. 2014

The Journal of Immunology

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Establishment of a human pro‐B cell line (JKB‐1) and its differentiation of preestablished bone marrow stromal cell layer

et al. 1994

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A human pro-B cell line, named JKB-1, was established from the bone marrow of a 16-year-old girl with acute lymphoblastic leukemia (ALL) in relapse. The origin of the JKB-1 cell line was indicated by its chromosomal and immunologic similarity to the patient's fresh leukemic cells. This cell line has been growing for more than 14 months in suspension culture medium and had a doubling time of about 24 hours. JKB-1 expressed terminal deoxynucleotide transferase (TdT) and early antigens (HLA-DR, CD19, CD24) of B cells, with heavy chain gene rearrangement. However, it did not express late antigens (CD10, CD20, CD21, CD22, CD23) of B cells, light chain gene rearrangement, and cytoplasmic mu-chain. These results suggested that JKB-1 is at the stage of "pro-B" cell or early B-cell precursors. This cell line was induced to differentiate after 7 days of co-incubation with irradiated bone marrow stromal cells because of the expression of pre-B cell antigens (CD10, CD20), cytoplasmic mu-chain, light chain gene rearrangement, and disappearance of TdT, JKB-1 cells adhered to a preestablished bone marrow stromal cell layer with string-like processes under scanning electron microscope. When JKB-1 cells were separated from the stromal layer by a cyclopore membrane with 0.45 micron pore size, they did not differentiate. Bone marrow stromal cell conditioned medium could not induce differentiation either. Thus it was suspected that direct contact between JKB-1 cells and stromal cells was required for differentiation. In methylcellulose semisolid medium, the colony size and number of JKB-1 cells were increased by stem cell factor (SCF), or interleukin (IL)-3, or IL-7, but they were decreased by IL-6. Moreover, SCF synergized with IL-3 or IL-7 to stimulate the proliferation of JKB-1 cells. Because there are very few reproducible models for examining early stages of human B-cell differentiation, the JKB-1 cell line would be useful for studying the relationship between human B-cell differentiation and bone marrow microenvironment, as well as leukemogenesis.

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The chemokine SDF‐1, stromal cell‐derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4

Rolink²,

et al. 1997

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In the bone marrow, progenitor (pro-) and precursor (pre-) B cells depend on close contact with stromal cells for growth and maturation. Stromal cell-derived factor 1 (SDF-1), also known as pre-B cell growth-stimulating factor, is produced by bone marrow stromal cells and was reported to act together with interleukin-7 as co-mitogen for pre-B cells. SDF-1 was recently shown to be a chemokine which is chemotactic for different types of leukocytes and acts via the chemokine receptor CXCR4. Using sorted B220+ bone marrow cells and several B cell lines characteristic for different stages of B lymphopoiesis, we now show that SDF-1 is a potent attractant for pro- and pre-B cells, but is inactive on B cells at later stages of development. In early B cell precursors, SDF-1 induced intracellular Ca2+ mobilization and in vitro migration with a potency and efficacy similar to that observed for chemokines acting on blood leukocytes. These responses were mediated via CXCR4 as they could be inhibited by an antireceptor antibody. SDF-1 is the first chemokine shown to act on early-stage B cell precursors. Mice lacking SDF-1 die perinatally and show a severe deficiency in B lymphopoiesis. We propose that SDF-1 released from the stromal cells exerts its critical hematopoietic function by selectively attracting and confining early B cell precursors within the bone marrow microenvironment that provides the necessary factors for growth and differentiation.

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Monoclonal antibodies that block adhesion of B cell progenitors to bone marrow stroma in vitro prevent B cell differentiation in vivo

Cited by 8 publications

References 46 publications

A Feeder-Free Differentiation System Identifies Autonomously Proliferating B Cell Precursors in Human Bone Marrow

A Feeder-Free Differentiation System Identifies Autonomously Proliferating B Cell Precursors in Human Bone Marrow

Establishment of a human pro‐B cell line (JKB‐1) and its differentiation of preestablished bone marrow stromal cell layer

The chemokine SDF‐1, stromal cell‐derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4

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