Essential Role for Survivin in the Proliferative Expansion of Progenitor and Mature B Cells
| Autor: | Julia Jellusova, Edward M. Conway, Ana V. Miletic, G. V. Baracho, Charlotte R. Lee, Robert C. Rickert, Matthew H. Cato |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Cell division Genotype Cell Survival Cellular differentiation Survivin Immunology Gene Expression Apoptosis Mice Transgenic Biology Inhibitor of apoptosis Lymphocyte Activation Article Immunophenotyping Inhibitor of Apoptosis Proteins 03 medical and health sciences Mice B cell homeostasis medicine Immunology and Allergy Animals Progenitor cell Mitosis neoplasms B cell Alleles B-Lymphocytes Precursor Cells B-Lymphoid Cell Differentiation Cell biology Immunity Humoral Repressor Proteins 030104 developmental biology medicine.anatomical_structure Antibody Formation Cancer research Biomarkers DNA Damage |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 196(5) |
| ISSN: | 1550-6606 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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