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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3042-3050.
Prepublished online as a Blood First Edition Paper on December 21, 2004; DOI 10.1182/blood-2004-10-3873.
 Previous Article | Next Article 
Submitted October 6, 2004
Accepted December 10, 2004
CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival
Silvia Deaglio, Tiziana Vaisitti, Luciana Bergui, Lisa Bonello, Alberto L Horenstein, Luca Tamagnone, Laurence Boumsell, and Fabio Malavasi*
Department of Genetics, Biology and Biochemistry, University of Torino Medical School, Torino, Italy; Research Center on Experimental Medicine (CeRMS), University of Torino Medical School, Torino, Italy
Division of Hematology, University of Torino Medical School, Torino, Italy
Research Center on Experimental Medicine (CeRMS), University of Torino Medical School, Torino, Italy
Institute for Cancer Research and Treatment (IRCC), University of Torino Medical School, Torino, Italy
Research Unit 448, Faculty of Medicine, Institut National de la Sante et de la Recherche Medicale, Creteil, France
* Corresponding author; email: fabio.malavasi{at}unito.it.
This work addresses the question whether CD38, a negative prognostic marker in B-CLL, plays a role in neoplastic B cell growth and survival. We show that CD38+ B-CLL cells bind to murine fibroblasts transfected with the CD31 ligand. The interaction triggers an extensive remodeling of the B-CLL membrane, with relocalization of BCR/CD19 to the CD38/CD31 contact areas and it also increases cell survival and proliferation. A second event is the up-modulation of the survival receptor CD100, restricted to proliferating cells, and a concomitant decrease of CD72 (low-affinity CD100 ligand and negative regulator of immune responses). The most efficient signals are delivered through sequential interactions between CD38/CD31 and CD100/plexin-B1 (high-affinity CD100 ligand), as inferred by co-culture experiments using specific transfectants and blocking mAbs. The finding that nurselike cells from B-CLL patients express CD31 and plexin-B1, which deliver growth and survival signals to CD38+/CD100+ B-CLL cells, further confirms the model proposed. These findings show that a set of normal receptors and ligands ruling physiologic signaling pathways in B lymphocytes becomes detrimental when expressed in the context of B-CLL cells, ultimately leading to the generation of a tumor reservoir.
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