title: Essential Role for Survivin in the Proliferative Expansion of Progenitor and Mature B Cells.
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.
authors.affiliation: Tumor Microenvironment and Cancer Immunology Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037; and.
authors.forename: Ana V
authors.identifier: http://orcid.org/0000-0002-9387-5652
authors.initials: AV
authors.lastname: Miletic
authors.affiliation: Tumor Microenvironment and Cancer Immunology Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037; and.
authors.forename: Julia
authors.initials: J
authors.lastname: Jellusova
authors.affiliation: Tumor Microenvironment and Cancer Immunology Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037; and.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Cato
authors.affiliation: Tumor Microenvironment and Cancer Immunology Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037; and.
authors.forename: Charlotte R
authors.initials: CR
authors.lastname: Lee
authors.affiliation: Tumor Microenvironment and Cancer Immunology Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037; and.
authors.forename: Gisele V
authors.identifier: http://orcid.org/0000-0001-6687-6468
authors.initials: GV
authors.lastname: Baracho
authors.affiliation: Center for Blood Research, Faculty of Medicine, University of British Columbia, Vancouver V6T 1Z3, British Columbia, Canada.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Conway
authors.affiliation: Tumor Microenvironment and Cancer Immunology Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037; and robert@SBPdiscovery.org.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Rickert
mesh_terms: D000483:Alleles; D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D017209:Apoptosis / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004249:DNA Damage; D015870:Gene Expression; D005838:Genotype; D056724:Immunity, Humoral / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*; D000077022:Survivin
chemical_list: D015415:Biomarkers; C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; D000077022:Survivin
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