The Journal of Experimental Medicine
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Published 5 January 2004. doi:10.1084/jem.20031104
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 1, 47-58
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Inflammation Controls B Lymphopoiesis by Regulating Chemokine CXCL12 Expression

Yoshihiro Ueda, Kaiyong Yang, Sandra J. Foster, Motonari Kondo and Garnett Kelsoe

Department of Immunology, Duke University Medical Center, Durham, NC 27710

Address correspondence to Garnett Kelsoe, Dept. of Immunology, Box 3010, Duke University Medical Center, Durham, NC 27710. Phone: (919) 613-7815; Fax: (919) 613-7878; email: ghkelsoe{at}duke.edu

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} (TNF{alpha}), 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 TNF{alpha} are potentiated by interleukin 1 ß (IL-1ß), 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-1ß 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 TNF{alpha} and IL-1ß transiently specialize the BM to support acute granulocytic responses and consequently promote extramedullary lymphopoiesis.

Key Words: bone marrow • innate immunity • TNF{alpha} • hematopoiesis • neutrophilia


Y. Ueda and K. Yang contributed equally to this work.

The online version of this article includes supplemental material.

Abbreviations used in this paper: CFU-B, pre–B cell CFU; NP-CGG, (4-hydroxy-3-nitrophenyl)acetyl-chicken {gamma} globulin; PTX, pertussis toxin; SA, streptavidin.


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