The B-cell receptor in control of tumor B-cell fitness: Biology and clinical relevance

Stefano Casola, Laura Perucho, Claudio Tripodo, Paola Sindaco, Maurilio Ponzoni, Fabio Facchetti

Research output: Contribution to journalReview articlepeer-review

Abstract

Surface expression of a functional B cell antigen receptor (BCR) is essential for the survival and proliferation of mature B cells. Most types of B-cell lymphoproliferative disorders retain surface BCR expression, including B-cell non-Hodgkin lymphomas (B-NHL) and chronic lymphocytic leukemia (CLL). Targeting BCR effectors in B-NHL cell lines in vitro has indicated that this signaling axis is crucial for malignant B cell growth. This has led to the development of inhibitors of BCR signaling, which are currently used for the treatment of CLL and several B-NHL subtypes. Recent studies based on conditional BCR inactivation in a MYC-driven mouse B-cell lymphoma model have revisited the role of the BCR in MYC-expressing tumor B cells. Indeed, lymphoma cells losing BCR expression continue to grow unless subjected to competition with their BCR-expressing counterparts, which causes their elimination. Here, we discuss the molecular nature of the fitness signal delivered by the BCR to MYC-expressing malignant B cells, ensuring their preferential persistence within a rapidly expanding tumor population. We also review growing evidence of Ig-negative cases belonging to several B-NHL subtypes and CLL, and discuss the clinical implications of these findings in relation to an emerging picture of clinical resistances to anti-BCR therapies.

Original languageEnglish
Pages (from-to)198-213
Number of pages16
JournalImmunological Reviews
Volume288
Issue number1
DOIs
Publication statusPublished - Mar 2019

Keywords

  • B-cell receptor
  • BCR inhibitors
  • c-MYC
  • lymphoma
  • lymphoma resistance
  • tumor cell fitness

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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