Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression.
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.
Type
Journal articleSubject
Adoptive TransferAnimals
Antigens, CD
B-Lymphocytes
Bone Marrow Cells
Chemokine CXCL12
Chemokines, CXC
Colony-Forming Units Assay
Female
Gene Expression Regulation
Inflammation
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Tumor Necrosis Factor
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Stromal Cells
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https://hdl.handle.net/10161/10909Published Version (Please cite this version)
10.1084/jem.20031104Publication Info
Ueda, Yoshihiro; Yang, Kaiyong; Foster, Sandra J; Kondo, Motonari; & Kelsoe, Garnett (2004). Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression. J Exp Med, 199(1). pp. 47-58. 10.1084/jem.20031104. Retrieved from https://hdl.handle.net/10161/10909.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Garnett H. Kelsoe
James B. Duke Distinguished Professor of Immunology
1. Lymphocyte development and antigen-driven diversification of immunoglobulin and
T cell antigen receptor genes. 2. The germinal center reaction and mechanisms for
clonal selection and self - tolerance. The origins of autoimmunity. 3. Interaction
of innate- and adaptive immunity and the role of inflammation in lymphoid organogenesis.
4. The role of secondary V(D)J gene rearrangment in lymphocyte development and malignancies.
5. Mathematical modeling of immune responses,

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