Impaired Expression of Rearranged Immunoglobulin Genes and Premature p53 Activation Block B Cell Development in BMI1 Null Mice.
Cell Rep
; 26(1): 108-118.e4, 2019 01 02.
Article
em En
| MEDLINE
| ID: mdl-30605667
ABSTRACT
B cell development is a highly regulated process that requires stepwise rearrangement of immunoglobulin genes to generate a functional B cell receptor (BCR). The polycomb group protein BMI1 is required for B cell development, but its function in developing B cells remains poorly defined. We demonstrate that BMI1 functions in a cell-autonomous manner at two stages during early B cell development. First, loss of BMI1 results in a differentiation block at the pro-B cell to pre-B cell transition due to the inability of BMI1-deficient cells to transcribe newly rearranged Igh genes. Accordingly, introduction of a pre-rearranged Igh allele partially restored B cell development in Bmi1-/- mice. In addition, BMI1 is required to prevent premature p53 signaling, and as a consequence, Bmi1-/- large pre-B cells fail to properly proliferate. Altogether, our results clarify the role of BMI1 in early B cell development and uncover an unexpected function of BMI1 during VDJ recombination.
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Base de dados:
MEDLINE
Assunto principal:
Genes de Imunoglobulinas
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Linfócitos B
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Rearranjo Gênico do Linfócito B
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Proteína Supressora de Tumor p53
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Proteínas Proto-Oncogênicas
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Complexo Repressor Polycomb 1
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article