CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival

Luca Tamagnone, Silvia Deaglio, Tiziana Vaisitti, Luciana Bergui, Lisa Bonello, Alberto L. Horenstein, Laurence Boumsell, Fabio Malavasi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

160 Citazioni (Scopus)

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. © 2005 by The American Society of Hematology.
Lingua originaleEnglish
pagine (da-a)3042-3050
Numero di pagine9
RivistaBlood
Volume105
DOI
Stato di pubblicazionePubblicato - 2005

Keywords

  • B-CLL
  • CD100
  • CD38
  • LYMPHOCYTIC LEUKEMIA

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