Journal of Leukocyte Biology
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Published online before print May 13, 2008
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1207841

Received for publication December 18, 2007.
Revised April 11, 2008.
Accepted for publication April 14, 2008.

Article

Pivotal Advance: IgE accelerates in vitro development of mast cells and modifies their phenotype

Jun-ichi Kashiwakura *, Wenbin Xiao *, Jiro Kitaura *, Yuko Kawakami *, Mari Maeda-Yamamoto {dagger}, Janet R. Pfeiffer {ddagger}, Bridget S. Wilson {ddagger}, Ulrich Blank {sect}, and Toshiaki Kawakami *@

*Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA; {dagger}National Research Institute of Vegetables and Tea Science, National Agriculture Research Organization, Shizuoka, Japan; {ddagger}Department of Pathology and Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA; and {sect}Inserm U699 and Université Paris 7-Diderot, Faculté de Médecine, Site Xavier Bichat, Paris, France

@ To whom correspondence should be addressed. E-mail: toshi{at}liai.org.


  Abstract

Antigen-dependent activation of IgE-bound mast cells is critical for immediate hypersensitivity and other allergic disorders. Recent studies have revealed the effects of monomeric IgEs on mast cell survival and activation. Furthermore, IgE molecules exhibit a wide range of heterogeneity in the ability to induce mast cell activation in the absence of antigen. Highly cytokinergic (HC) IgEs can induce a variety of activation events including cell survival, degranulation, cytokine production, and migration, whereas poorly cytokinergic (PC) IgEs can do so inefficiently. Here, we show that culture of bone marrow cells in the presence of monomeric IgEs results in an increased number of mast cells compared with cultures grown without IgE. Furthermore, time in culture required to generate ≥80% pure mast cells is decreased. IgE molecules can directly influence mast cell progenitors to differentiate into mast cells. mRNA expression of several mast cell proteases and mast cell-related transcription factors is higher in mast cells cultured with a HC IgE than those cultured with a PC IgE or without IgE. Expression of early growth response factor-1, a transcription factor that is involved in the production of TNF-{alpha} in mast cells, is enhanced in cultures containing high and low concentrations of HC IgE and a high concentration of PC IgE. Consistent with this, expression of TNF-{alpha} is higher in mast cells cultured with HC IgE than PC IgE. Therefore, our results suggest that monomeric IgEs, especially HC IgEs, not only promote mast cell development but also modulate the mast cell phenotype.

Key Words: highly cytokinergic • poorly cytokinergic • differentiation • TNF


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