Age-associated alterations in CXCL1 chemokine expression by murine B cells.
BACKGROUND
The CXCL1 chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC), have been shown to play a role in a number of pathophysiological disease states including endotoxin-induced inflammation and bacterial meningitis. While the expression of these chemokines has been identified in a variety of cell types in the mouse, little is known about their expression with murine B-lymphocytes.


RESULTS
Here, we demonstrate that highly purified murine splenic B cells are capable of expressing both MIP-2 and KC protein and mRNA upon activation with lipopolysaccharide (LPS) but not in response to anti-micro and anti-CD40 in combination with interleukin-4 (IL-4) stimulation. Moreover, these chemokines are expressed at higher levels in B cells derived from young (4 m) compared to old (24-29 m) mice. Upon fractionation into distinct B-cell subsets, we found that the expression of MIP-2 and KC by aged follicular (FO) B cells is significantly decreased when compared to the same cells from younger mice, while only MIP-2 production was found to be diminished in aged marginal zone (MZ) B cells. Interestingly, MIP-2 and KC production by newly formed (NF) B cells did not significantly differ with age. Moreover, the potential relevance of these findings is supported by the poor ability of LPS-activated aged B cells to specifically mediate CXCL1-dependent leukocyte recruitment when compared to younger B cells.


CONCLUSIONS
Overall, the decreased expression of CXCL1 chemokines by aged B cells in response to LPS may have potential implications on the secondary recruitment of leukocytes to sites of microbial infections and inflammation possibly contributing to the increased susceptibility of older subjects to pathogen challenge.
Gerontology Research Center, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA. lhu6@jhmi.edu
Lina
L
Hu
Vishwa Deep
VD
Dixit
Valeria
V
de Mello-Coelho
Dennis D
DD
Taub
D000375:Aging / Q000276:immunology*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis*; D019743:Chemokines, CXC / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D007075:Immunoglobulin M; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides