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GNA13 loss in germinal center B cells leads to impaired apoptosis and promotes lymphoma in vivo.
- Source :
-
Blood . 6/2/2016, Vol. 127 Issue 22, p2723-2731. 9p. - Publication Year :
- 2016
-
Abstract
- GNA13 is the most frequently mutated gene in germinal center (GC)-derived B-cell lymphomas, including nearly a quarter of Burkitt lymphoma and GC-derived diffuse large B-cell lymphoma. These mutations occur in a pattern consistent with loss of function. We have modeled the GNA13-deficient state exclusively in GC B cells by crossing the Gna13 conditional knockout mouse strain with the GC-specific AID-Cre transgenic strain. AID-Cre+ GNA13-deficient mice demonstrate disordered GC architecture and dark zone/ light zone distribution in vivo, and demonstrate altered migration behavior, decreased levels of filamentous actin, and attenuated RhoA activity in vitro. We also found that GNA13-deficient mice have increased numbers of GC B cells that display impaired caspase-mediated cell death and increased frequency of somatic hypermutation in the immunoglobulin VH locus. Lastly, GNA13 deficiency, combined with conditional MYC transgene expression in mouse GC B cells, promotes lymphomagenesis. Thus, GNA13 loss is associated with GC B-cell persistence, in which impaired apoptosis and ongoing somatic hypermutation may lead to an increased risk of lymphoma development. [ABSTRACT FROM AUTHOR]
- Subjects :
- *G proteins
*GENETIC mutation
*GERMINAL centers
*B cell lymphoma
*APOPTOSIS
*GENETICS
Subjects
Details
- Language :
- English
- ISSN :
- 00064971
- Volume :
- 127
- Issue :
- 22
- Database :
- Academic Search Index
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 115868979
- Full Text :
- https://doi.org/10.1182/blood-2015-07-659938