Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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A more recent version of this article appeared on September 1, 2007

Published online before print June 15, 2007
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0706481

Received for publication July 29, 2006.
Revised April 3, 2007.
Accepted for publication May 11, 2007.

Article

Critical role of monocytes to support normal B cell and diffuse large B cell lymphoma survival and proliferation

Chris G. Mueller *{dagger}@, Charlotte Boix {dagger}, Wing-Hong Kwan {dagger}, Cécile Daussy {dagger}, Emilie Fournier {dagger}, Wolf H. Fridman {dagger}, and Thierry J. Molina {ddagger}

*CNRS, Laboratory of Therapeutic Immunology and Chemistry, IBMC, Strasbourg, France; {dagger}INSERM, Centre de Recherches Biomédicales des Cordeliers, Université Pierre et Marie Curie (Paris VI) et René Descartes (Paris V), Paris, France; and {ddagger}Université Paris-Descartes, Faculté de Médecine, AP-HP, Hôtel-Dieu, Service d’Anatomie et de Cytologie Pathologiques, Paris, France

@ To whom correspondence should be addressed. E-mail: c.mueller{at}ibmc.u-strasbg.fr.


  Abstract

Large B cell lymphomas can comprise numerous CD14+ cells in the tumor stroma, which raises the question of whether monocytes can support B cell survival and proliferation. We show that the coculture of monocytes with B cells from peripheral blood or from diffuse large B cell lymphoma enabled prolonged B cell survival. Under these conditions, diffuse large lymphoma B cells proliferated, and addition of B cell-activating factor of the TNF family and IL-2 enhanced cell division. Monocytes and dendritic cells (DC) had similar antiapoptotic activity on healthy B cells but displayed differences with respect to B cell proliferation. Monocytes and cord blood-derived CD14+ cells promoted B cell proliferation in the presence of an anti-CD40 stimulus, whereas DC supported B cell proliferation when activated through the BCR. DC and CD14+ cells were able to induce plasmocyte differentiation. When B cells were activated via the BCR or CD40, they released the leukocyte attractant CCL5, and this chemokine is one of the main chemokines expressed in diffuse large B cell lymphoma. The data support the notion that large B cell lymphoma recruit monocytes via CCL5 to support B cell survival and proliferation.

Key Words: macrophages • chemokines • tumor immunity






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Copyright © 2007 by the Society for Leukocyte Biology.