Regulation of Constitutive Bone Marrow Cell Proliferation by Bone Marrow Suppressor Cells

Soderberg, Lee S. F.

doi:10.1159/000233565

Cited by 7 publications

(2 citation statements)

References 10 publications

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“…One of these was adherent, and had macrophage-like morphology (61), similar to the suppressive cells that we found within the CD11b + myeloid fraction, potentially MDSCs. The other suppressor cells were described as non-adherent, FcRγ+, complement receptor negative, and were thought to be suppressor lymphocytes (61, 62). If so, based on current knowledge, these cells could be Treg cells, IL-10-producing Bregs (63), or inflammatory TNF-producing aged B cells (ABCs) (27).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Changes in Bone Marrow Microenvironment Associated with Declining B Lymphopoiesis

Kennedy

Knight

2017

The Journal of Immunology

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B lymphopoiesis arrests precipitously in rabbits such that by 2 to 4 months of age, prior to sexual maturity, little to no B lymphopoiesis occurs in the bone marrow (BM). Previously, we showed that in mice, adipocytes inhibit B lymphopoiesis in vitro by inducing inflammatory myeloid cells which produce IL-1β. Here, we characterized rabbit BM after the arrest of B lymphopoiesis and found a dramatic increase in fat, increased CD11b+ myeloid cells, and upregulated expression of the inflammatory molecules, IL-1β and S100A9 by the myeloid cells. We added BM fat, CD11b+ myeloid cells, and recombinant S100A9 to B lymphopoiesis cultures and found that they inhibited B lymphopoiesis and enhanced myelopoiesis. Unlike IL-1β which inhibits B lymphopoiesis by acting on early lymphoid progenitors, S100A9 inhibits B lymphopoiesis by acting on myeloid cells and promoting the release of inflammatory molecules, including IL-1β. Many molecules produced by adipocytes activate the NLRP3 inflammasome, and the NLRP3 inhibitor, glybenclamide restored B lymphopoiesis and minimized induction of myeloid cells induced by adipocyte-conditioned medium in vitro. We suggest that fat provides an inflammatory microenvironment in the BM, and promotes/activates myeloid cells to produce inflammatory molecules such as IL-1β and S100A9, which negatively regulate B lymphopoiesis.

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Section: Discussionmentioning

confidence: 99%

Inflammatory Changes in Bone Marrow Microenvironment Associated with Declining B Lymphopoiesis

Kennedy

Knight

2017

The Journal of Immunology

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“…Several years ago, Soderberg and colleagues (1984a, 1984b) identified two types of suppressor cells in rabbit BM, one of which may be similar to the recently-identified MDSCs. The first suppressive cell, an adherent macrophage-like population inhibited proliferation and activation of BM cells after immune complex stimulation.…”

Section: Age-related Changes To the Bm Microenvironmentmentioning

confidence: 72%

Bone marrow fat and the decline of B lymphopoiesis in rabbits

Kennedy

Witte

Knight

2016

Developmental & Comparative Immunology

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B lymphopoiesis is necessary to generate a diverse pool of naïve B cells that are able to respond to a broad spectrum of antigens during immune responses to pathogens and to vaccination. Rabbits have been utilized for many years to generate high affinity monoclonal and polyclonal antibodies. Specific antibodies generated in rabbits have greatly advanced scientific discoveries, but the unique qualities of rabbit B cell development have been underappreciated. Unlike in humans and mice, where B lymphopoiesis declines in mid to late life, B lymphopoiesis in rabbits arrests early in life, between 2–4 months of age. This review focuses on the early loss of B cell development in rabbits and the contribution of the bone marrow microenvironment to this process. We also propose directions for future research in this area, and discuss how the rabbit can be used as a model to understand the decline of B lymphopoiesis that occurs in humans late in life. Such studies will be important for developing therapeutics targeted to prevent and/or reverse declining B lymphopoiesis in the elderly, as well as boosting immunity and antibody responses after infection or vaccination.

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Transforming growth factor-β is the major mediator of natural suppressor cells derived from normal bone marrow

Moore

Shaw²,

Soderberg³

1992

Journal of Leukocyte Biology

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We previously reported that murine bone marrow cells activated by interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) had potent nonspecific natural suppressor (NS) cell activity. In the present study, we demonstrated that these activated NS cells released a soluble factor (or factors) capable of nonspecifically inhibiting T cell mitogenic responses. Consistent with the properties of transforming growth factor-beta (TGF-beta), treatment of the NS supernates with heat failed to denature the factor, and in fact significantly increased its suppressive activity. The NS suppressor factor strongly inhibited proliferation of the TGF-beta-sensitive tumor cell line, A549. Cytokine activation of suppressive activity correlated with the production of a 10- to 13-kDa protein, consistent with the size of TGF-beta and rIL-3 induced a sevenfold increase in TGF-beta transcription. Finally, neutralizing anti-TGF-beta antibody inhibited the suppressive activity of the supernates, indicating that TGF-beta was responsible for most, if not all, of the suppression expressed by these bone marrow NS cells.

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Regulation of Constitutive Bone Marrow Cell Proliferation by Bone Marrow Suppressor Cells

Cited by 7 publications

References 10 publications

Inflammatory Changes in Bone Marrow Microenvironment Associated with Declining B Lymphopoiesis

Inflammatory Changes in Bone Marrow Microenvironment Associated with Declining B Lymphopoiesis

Bone marrow fat and the decline of B lymphopoiesis in rabbits

Transforming growth factor-β is the major mediator of natural suppressor cells derived from normal bone marrow

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