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Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression.

Ueda Y, Yang K, Foster SJ, Kondo M, Kelsoe G - J. Exp. Med. (2004)

Bottom Line: Mobilization reflects a reduced CXCL12 message and protein in BM and changes to the BM environment that prevents homing by cells from naive donors.The effects of TNFalpha are potentiated by interleukin 1 beta (IL-1beta), which acts primarily to expand the BM granulocyte compartment.We propose that TNFalpha and IL-1beta transiently specialize the BM to support acute granulocytic responses and consequently promote extramedullary lymphopoiesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Box 3010, Duke University Medical Center, Durham, NC 27710, USA.

ABSTRACT
Inflammation removes developing and mature lymphocytes from the bone marrow (BM) and induces the appearance of developing B cells in the spleen. BM granulocyte numbers increase after lymphocyte reductions to support a reactive granulocytosis. Here, we demonstrate that inflammation, acting primarily through tumor necrosis factor alpha (TNFalpha), mobilizes BM lymphocytes. Mobilization reflects a reduced CXCL12 message and protein in BM and changes to the BM environment that prevents homing by cells from naive donors. The effects of TNFalpha are potentiated by interleukin 1 beta (IL-1beta), which acts primarily to expand the BM granulocyte compartment. Our observations indicate that inflammation induces lymphocyte mobilization by suppressing CXCL12 retention signals in BM, which, in turn, increases the ability of IL-1beta to expand the BM granulocyte compartment. Consistent with this idea, lymphocyte mobilization and a modest expansion of BM granulocyte numbers follow injections of pertussis toxin. We propose that TNFalpha and IL-1beta transiently specialize the BM to support acute granulocytic responses and consequently promote extramedullary lymphopoiesis.

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PTX elicits BM lymphopenia and mobilizes CD93+B220loIgM− cells. BM, blood (BL), and spleen (SPL) cells were harvested from BL/6 mice 0–24 d after injection of 300–500 ng PTX and analyzed by flow cytometry. (A) Dynamics of BM B cell subsets (left) and granulocytes (right). Points represent mean ± SEM numbers of B220lo (•), B220hi (▪), and Gr-1+ (⋄) cells from two femurs. (B) Appearance of CD93+B220loIgM− cells in the periphery after PTX treatment. FACS® profiles of CD93+B220lo and CD93−B220lo cells from BL and SPL in PBS- and PTX-treated mice are shown. Percentages of cells in the CD93+B220lo gate are indicated. (C) PTX elicits populations of CD93+B220loIgM− cells in BL and SPL. Representative FACS® profiles of surface IgM expression by CD93+B220lo cells. Shaded areas, solid lines, and dashed lines represent surface IgM expression by CD93+B220lo, CD93−B220hi, and B220− cells, respectively. Percentages of IgM+ cells in CD93+B220lo cell gates are shown.
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fig8: PTX elicits BM lymphopenia and mobilizes CD93+B220loIgM− cells. BM, blood (BL), and spleen (SPL) cells were harvested from BL/6 mice 0–24 d after injection of 300–500 ng PTX and analyzed by flow cytometry. (A) Dynamics of BM B cell subsets (left) and granulocytes (right). Points represent mean ± SEM numbers of B220lo (•), B220hi (▪), and Gr-1+ (⋄) cells from two femurs. (B) Appearance of CD93+B220loIgM− cells in the periphery after PTX treatment. FACS® profiles of CD93+B220lo and CD93−B220lo cells from BL and SPL in PBS- and PTX-treated mice are shown. Percentages of cells in the CD93+B220lo gate are indicated. (C) PTX elicits populations of CD93+B220loIgM− cells in BL and SPL. Representative FACS® profiles of surface IgM expression by CD93+B220lo cells. Shaded areas, solid lines, and dashed lines represent surface IgM expression by CD93+B220lo, CD93−B220hi, and B220− cells, respectively. Percentages of IgM+ cells in CD93+B220lo cell gates are shown.

Mentions: 3 d after injecting PTX, CD93+B220lo and CD93−B220hi BM cell numbers fell significantly and remained suppressed until day 12. B cell numbers began to recover 12–18 d after PTX treatment, reaching normal levels by day 24 (Fig. 8 A). PTX also lowered CD3+ BM cell numbers (Table I) with similar kinetics (unpublished data). These effects were dependent on the ribosyltransferase activity of PTX, as the enzymatically inactive PTX B oligomer had no effect on BM (Fig. S2, available at http://www.jem.org/cgi/content/full/jem.20031104/DC1). PTX had little effect on thymocyte populations (Table S1).


Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression.

Ueda Y, Yang K, Foster SJ, Kondo M, Kelsoe G - J. Exp. Med. (2004)

PTX elicits BM lymphopenia and mobilizes CD93+B220loIgM− cells. BM, blood (BL), and spleen (SPL) cells were harvested from BL/6 mice 0–24 d after injection of 300–500 ng PTX and analyzed by flow cytometry. (A) Dynamics of BM B cell subsets (left) and granulocytes (right). Points represent mean ± SEM numbers of B220lo (•), B220hi (▪), and Gr-1+ (⋄) cells from two femurs. (B) Appearance of CD93+B220loIgM− cells in the periphery after PTX treatment. FACS® profiles of CD93+B220lo and CD93−B220lo cells from BL and SPL in PBS- and PTX-treated mice are shown. Percentages of cells in the CD93+B220lo gate are indicated. (C) PTX elicits populations of CD93+B220loIgM− cells in BL and SPL. Representative FACS® profiles of surface IgM expression by CD93+B220lo cells. Shaded areas, solid lines, and dashed lines represent surface IgM expression by CD93+B220lo, CD93−B220hi, and B220− cells, respectively. Percentages of IgM+ cells in CD93+B220lo cell gates are shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1887733&req=5

fig8: PTX elicits BM lymphopenia and mobilizes CD93+B220loIgM− cells. BM, blood (BL), and spleen (SPL) cells were harvested from BL/6 mice 0–24 d after injection of 300–500 ng PTX and analyzed by flow cytometry. (A) Dynamics of BM B cell subsets (left) and granulocytes (right). Points represent mean ± SEM numbers of B220lo (•), B220hi (▪), and Gr-1+ (⋄) cells from two femurs. (B) Appearance of CD93+B220loIgM− cells in the periphery after PTX treatment. FACS® profiles of CD93+B220lo and CD93−B220lo cells from BL and SPL in PBS- and PTX-treated mice are shown. Percentages of cells in the CD93+B220lo gate are indicated. (C) PTX elicits populations of CD93+B220loIgM− cells in BL and SPL. Representative FACS® profiles of surface IgM expression by CD93+B220lo cells. Shaded areas, solid lines, and dashed lines represent surface IgM expression by CD93+B220lo, CD93−B220hi, and B220− cells, respectively. Percentages of IgM+ cells in CD93+B220lo cell gates are shown.
Mentions: 3 d after injecting PTX, CD93+B220lo and CD93−B220hi BM cell numbers fell significantly and remained suppressed until day 12. B cell numbers began to recover 12–18 d after PTX treatment, reaching normal levels by day 24 (Fig. 8 A). PTX also lowered CD3+ BM cell numbers (Table I) with similar kinetics (unpublished data). These effects were dependent on the ribosyltransferase activity of PTX, as the enzymatically inactive PTX B oligomer had no effect on BM (Fig. S2, available at http://www.jem.org/cgi/content/full/jem.20031104/DC1). PTX had little effect on thymocyte populations (Table S1).

Bottom Line: Mobilization reflects a reduced CXCL12 message and protein in BM and changes to the BM environment that prevents homing by cells from naive donors.The effects of TNFalpha are potentiated by interleukin 1 beta (IL-1beta), which acts primarily to expand the BM granulocyte compartment.We propose that TNFalpha and IL-1beta transiently specialize the BM to support acute granulocytic responses and consequently promote extramedullary lymphopoiesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Box 3010, Duke University Medical Center, Durham, NC 27710, USA.

ABSTRACT
Inflammation removes developing and mature lymphocytes from the bone marrow (BM) and induces the appearance of developing B cells in the spleen. BM granulocyte numbers increase after lymphocyte reductions to support a reactive granulocytosis. Here, we demonstrate that inflammation, acting primarily through tumor necrosis factor alpha (TNFalpha), mobilizes BM lymphocytes. Mobilization reflects a reduced CXCL12 message and protein in BM and changes to the BM environment that prevents homing by cells from naive donors. The effects of TNFalpha are potentiated by interleukin 1 beta (IL-1beta), which acts primarily to expand the BM granulocyte compartment. Our observations indicate that inflammation induces lymphocyte mobilization by suppressing CXCL12 retention signals in BM, which, in turn, increases the ability of IL-1beta to expand the BM granulocyte compartment. Consistent with this idea, lymphocyte mobilization and a modest expansion of BM granulocyte numbers follow injections of pertussis toxin. We propose that TNFalpha and IL-1beta transiently specialize the BM to support acute granulocytic responses and consequently promote extramedullary lymphopoiesis.

Show MeSH
Related in: MedlinePlus