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, Fabio Malavasi

Research output: Contribution to journalArticle

Abstract

This work addresses the question whether CD38, a negative prognostic marker in B-cell chronic lymphocytic leukemia (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 coculture experiments using specific transfectants and blocking monoclonal antibodies (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.

Original languageEnglish
Pages (from-to)3042-3050
Number of pages9
JournalBlood
Volume105
Issue number8
DOIs
Publication statusPublished - Apr 15 2005

ASJC Scopus subject areas

  • Hematology

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    Deaglio, S., Vaisitti, T., Bergui, L., Bonello, L., Horenstein, A. L., Tamagnone, L., Boumsell, L., & Malavasi, F. (2005). CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival. Blood, 105(8), 3042-3050. https://doi.org/10.1182/blood-2004-10-3873