Critical role of monocytes to support normal B cell and diffuse large B cell lymphoma survival and proliferation.
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 (BAFF) 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.
Mueller
Chris G
CG
INSERM, U872, Centre de Recherches Biomédicales des Cordeliers Université Pierre et Marie Curie (Paris VI) et René Descartes (Paris V), UMR S 872, Paris, France. c.mueller@ibmc.u-strasbg.fr.
Boix
Charlotte
C
Kwan
Wing-Hong
WH
Daussy
Cécile
C
Fournier
Emilie
E
Fridman
Wolf H
WH
Molina
Thierry J
TJ
D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D018946:Chemokine CCL5; D019742:Chemokines, CC / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D007376:Interleukin-2 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000473:pathology; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D022423:Myeloid Cells / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053265:B-Cell Activation Factor Receptor; D014408:Biomarkers, Tumor; C483024:CCL5 protein, human; D019013:CD40 Antigens; D018946:Chemokine CCL5; D019742:Chemokines, CC; D007376:Interleukin-2; D018950:Lipopolysaccharide Receptors