Journal article
Deletion of Rb1 induces both hyperproliferation and cell death in murine germinal center B cells
Experimental hematology, Vol.44(3), pp.161-165.e4
03/2016
DOI: 10.1016/j.exphem.2015.11.006
PMCID: PMC4789175
PMID: 26607597
Abstract
The retinoblastoma gene (RB1) has been implicated as a tumor suppressor in multiple myeloma (MM), yet its role remains unclear because in the majority of cases with 13q14 deletions, un-mutated RB1 remains expressed from the retained allele. To explore the role of Rb1 in MM, we examined the functional consequences of single- and double-copy Rb1 loss in germinal center B cells, the cells of origin of MM. We generated mice without Rb1 function in germinal center B cells by crossing Rb1(Flox/Flox) with C-γ-1-Cre (Cγ1) mice expressing the Cre recombinase in class-switched B cells in a p107(-/-) background to prevent p107 from compensating for Rb1 loss (Cγ1-Rb1(F/F)-p107(-/-)). All mice developed normally, but B cells with two copies of Rb1 deleted (Cγ1-Rb1(F/F)-p107(-/-)) exhibited increased proliferation and cell death compared with Cγ1-Rb1(+/+)-p107(-/-) controls ex vivo. In vivo, Cγ1-Rb1(F/F)-p107(-/-) mice had a lower percentage of splenic B220+ cells and reduced numbers of bone marrow antigen-specific secreting cells compared with control mice. Our data indicate that Rb1 loss induces both cell proliferation and death in germinal center B cells. Because no B-cell malignancies developed after 1 year of observation, our data also suggest that Rb1 loss is not sufficient to transform post-germinal center B cells and that additional, specific mutations are likely required to cooperate with Rb1 loss to induce malignant transformation.
Details
- Title: Subtitle
- Deletion of Rb1 induces both hyperproliferation and cell death in murine germinal center B cells
- Creators
- Zhiwen He - Washington University in St. LouisJulie O'Neal - Washington University in St. LouisWilliam C Wilson - Washington University in St. LouisNitin Mahajan - Washington University in St. LouisJun Luo - Washington University in St. LouisYinan Wang - Washington University in St. LouisMack Y Su - Washington University in St. LouisLan Lu - Washington University in St. LouisJames B Skeath - Washington University in St. LouisDeepta Bhattacharya - Washington University in St. LouisMichael H Tomasson - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Experimental hematology, Vol.44(3), pp.161-165.e4
- DOI
- 10.1016/j.exphem.2015.11.006
- PMID
- 26607597
- PMCID
- PMC4789175
- NLM abbreviation
- Exp Hematol
- ISSN
- 0301-472X
- eISSN
- 1873-2399
- Grant note
- R01 NS036570 / NINDS NIH HHS R01 CA175349 / NCI NIH HHS T32 CA113275 / NCI NIH HHS
- Language
- English
- Date published
- 03/2016
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984359799102771
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