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Pathway-selective suppression of chemokine receptor signaling in B cells by LPS through downregulation of PLC-β2

Cellular & Molecular Immunology volume 7, pages 428–439 (2010)Cite this article

Abstract

Lymphocyte activation leads to changes in chemokine receptor expression. There are limited data, however, on how lymphocyte activators can alter chemokine signaling by affecting downstream pathways. We hypothesized that B cell-activating agents might alter chemokine responses by affecting downstream signal transducers, and that such effects might differ depending on the activator. We found that activating mouse B cells using either anti-IgM or lipopolysaccharide (LPS) increased the surface expression of CCR6 and CCR7 with large increases in chemotaxis to their cognate ligands. By contrast, while anti-IgM also led to enhanced calcium responses, LPS-treated cells showed only small changes in calcium signaling as compared with cells that were freshly isolated. Of particular interest, we found that LPS caused a reduction in the level of B-cell phospholipase C (PLC)-β2 mRNA and protein. Data obtained using PLC-β2−/− mice showed that the β2 isoform mediates close to one-half the chemokine-induced calcium signal in resting and anti-IgM-activated B cells, and we found that calcium signals in the LPS-treated cells were boosted by increasing the level of PLC-β2 using transfection, consistent with a functional effect of downregulating PLC-β2. Together, our results show activator-specific effects on responses through B-cell chemokine receptors that are mediated by quantitative changes in a downstream signal-transducing protein, revealing an activity for LPS as a downregulator of PLC-β2, and a novel mechanism for controlling chemokine-induced signals in lymphocytes.

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Acknowledgements

We would like to thank Martin Dorf, Harvard Medical School, for providing the cDNA for mouse CXCR4; Kaimei Song, for sharing reagents; Paul Goldsmith, for help in making antibodies; and Sue Goo Rhee for advice and for supplying pMT2-PLC-β2. The Intramural Research Program of NIAID, NIH, supported this research.

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Authors and Affiliations

  1. Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Aiko-Konno Shirakawa, Fang Liao, Hongwei H Zhang, Michael N Hedrick, Satya P Singh & Joshua M Farber

  2. Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA

    Dianqing Wu

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  1. Aiko-Konno Shirakawa
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Correspondence to Joshua M Farber.

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Shirakawa, AK., Liao, F., Zhang, H. et al. Pathway-selective suppression of chemokine receptor signaling in B cells by LPS through downregulation of PLC-β2. Cell Mol Immunol 7, 428–439 (2010). https://doi.org/10.1038/cmi.2010.46

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