Essential Role for Survivin in the Proliferative Expansion of Progenitor and Mature B Cells

J Immunol. 2016 Mar 1;196(5):2195-204. doi: 10.4049/jimmunol.1501690. Epub 2016 Jan 25.

Abstract

Survivin is a member of the inhibitor of apoptosis family of proteins and a biomarker of poor prognosis in aggressive B cell non-Hodgkin's lymphoma. In addition to its role in inhibition of apoptosis, survivin also regulates mitosis. In this article, we show that deletion of survivin during early B cell development results in a complete block at the cycling pre-B stage. In the periphery, B cell homeostasis is not affected, but survivin-deficient B cells are unable to mount humoral responses. Correspondingly, we show that survivin is required for cell division in response to mitogenic stimulation. Thus, survivin is essential for proliferation of B cell progenitors and activated mature B cells, but is dispensable for B cell survival. Moreover, a small-molecule inhibitor of survivin strongly impaired the growth of representative B lymphoma lines in vitro, supporting the validity of survivin as an attractive therapeutic target for high-grade B cell non-Hodgkin's lymphoma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Animals
  • Antibody Formation / genetics
  • Antibody Formation / immunology
  • Apoptosis / genetics
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism*
  • Biomarkers
  • Cell Differentiation / genetics
  • Cell Survival / genetics
  • DNA Damage
  • Gene Expression
  • Genotype
  • Immunity, Humoral / genetics
  • Immunity, Humoral / immunology
  • Immunophenotyping
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors
  • Inhibitor of Apoptosis Proteins / deficiency
  • Inhibitor of Apoptosis Proteins / genetics*
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Transgenic
  • Precursor Cells, B-Lymphoid / cytology
  • Precursor Cells, B-Lymphoid / drug effects
  • Precursor Cells, B-Lymphoid / metabolism*
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / deficiency
  • Repressor Proteins / genetics*
  • Survivin

Substances

  • Biomarkers
  • Birc5 protein, mouse
  • Inhibitor of Apoptosis Proteins
  • Repressor Proteins
  • Survivin