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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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Immunization depletes BM B cells but increases BM granulocyte numbers. BL/6 mice were immunized with NP-CGG/IFA. Lymphocytes and granulocytes from femur and tibia were analyzed by flow cytometry; representative FACS® profiles of BM cells (A, B220 and CD93; C, B220 and Gr-1) 3 or 4 d after immunization. Percentages of gated CD93+B220lo, CD93−B220hi, and Gr-1+B220− cells are given. 3 d after immunization, CD93+B220lo and CD93−B220hi cell numbers fall in the BM (A), whereas Gr-1+B220− cell numbers change little (C). Dynamics of BM B cell (B) or granulocyte (D) populations indicate that B lymphopenia persists for ≥12 d (B), whereas granulocyte numbers increase (D). Points represent mean ± SEM of CD93+B220lo (•), CD93−B220hi (▪), and Gr-1+B220− cells (♦). Asterisks indicate significant differences from controls: *, P < 0.05; **, P < 0.01.
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fig1: Immunization depletes BM B cells but increases BM granulocyte numbers. BL/6 mice were immunized with NP-CGG/IFA. Lymphocytes and granulocytes from femur and tibia were analyzed by flow cytometry; representative FACS® profiles of BM cells (A, B220 and CD93; C, B220 and Gr-1) 3 or 4 d after immunization. Percentages of gated CD93+B220lo, CD93−B220hi, and Gr-1+B220− cells are given. 3 d after immunization, CD93+B220lo and CD93−B220hi cell numbers fall in the BM (A), whereas Gr-1+B220− cell numbers change little (C). Dynamics of BM B cell (B) or granulocyte (D) populations indicate that B lymphopenia persists for ≥12 d (B), whereas granulocyte numbers increase (D). Points represent mean ± SEM of CD93+B220lo (•), CD93−B220hi (▪), and Gr-1+B220− cells (♦). Asterisks indicate significant differences from controls: *, P < 0.05; **, P < 0.01.

Mentions: Immunization with NP-CGG/IFA reduces the numbers of developing (CD93+B220lo) and mature (CD93−B220hi; reference 24) BM B cells (Fig. 1 A); losses are evident 3 d after immunization, with maximal reductions coming on days 4–6 (CD93+B220lo B cells, four- to fivefold reductions; CD93−B220hi B cells, sevenfold) (Fig. 1 B). Thereafter, developing and mature B cell numbers in the BM return to normal levels (Fig. 1 B). Both B cell populations decline at similar rates, but losses of CD93−B220hi cells are significantly (P < 0.05) greater and more sustained than that of CD93+B220lo cells. Similar kinetics of loss and recovery are also observed for BM T cells (Table I and unpublished data), indicating that all BM lymphocyte populations are sensitive to adjuvant-induced depletion.


Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression.

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

Immunization depletes BM B cells but increases BM granulocyte numbers. BL/6 mice were immunized with NP-CGG/IFA. Lymphocytes and granulocytes from femur and tibia were analyzed by flow cytometry; representative FACS® profiles of BM cells (A, B220 and CD93; C, B220 and Gr-1) 3 or 4 d after immunization. Percentages of gated CD93+B220lo, CD93−B220hi, and Gr-1+B220− cells are given. 3 d after immunization, CD93+B220lo and CD93−B220hi cell numbers fall in the BM (A), whereas Gr-1+B220− cell numbers change little (C). Dynamics of BM B cell (B) or granulocyte (D) populations indicate that B lymphopenia persists for ≥12 d (B), whereas granulocyte numbers increase (D). Points represent mean ± SEM of CD93+B220lo (•), CD93−B220hi (▪), and Gr-1+B220− cells (♦). Asterisks indicate significant differences from controls: *, P < 0.05; **, P < 0.01.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Immunization depletes BM B cells but increases BM granulocyte numbers. BL/6 mice were immunized with NP-CGG/IFA. Lymphocytes and granulocytes from femur and tibia were analyzed by flow cytometry; representative FACS® profiles of BM cells (A, B220 and CD93; C, B220 and Gr-1) 3 or 4 d after immunization. Percentages of gated CD93+B220lo, CD93−B220hi, and Gr-1+B220− cells are given. 3 d after immunization, CD93+B220lo and CD93−B220hi cell numbers fall in the BM (A), whereas Gr-1+B220− cell numbers change little (C). Dynamics of BM B cell (B) or granulocyte (D) populations indicate that B lymphopenia persists for ≥12 d (B), whereas granulocyte numbers increase (D). Points represent mean ± SEM of CD93+B220lo (•), CD93−B220hi (▪), and Gr-1+B220− cells (♦). Asterisks indicate significant differences from controls: *, P < 0.05; **, P < 0.01.
Mentions: Immunization with NP-CGG/IFA reduces the numbers of developing (CD93+B220lo) and mature (CD93−B220hi; reference 24) BM B cells (Fig. 1 A); losses are evident 3 d after immunization, with maximal reductions coming on days 4–6 (CD93+B220lo B cells, four- to fivefold reductions; CD93−B220hi B cells, sevenfold) (Fig. 1 B). Thereafter, developing and mature B cell numbers in the BM return to normal levels (Fig. 1 B). Both B cell populations decline at similar rates, but losses of CD93−B220hi cells are significantly (P < 0.05) greater and more sustained than that of CD93+B220lo cells. Similar kinetics of loss and recovery are also observed for BM T cells (Table I and unpublished data), indicating that all BM lymphocyte populations are sensitive to adjuvant-induced depletion.

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