期刊
NATURE COMMUNICATIONS
卷 4, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms2334
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资金
- National Institutes of Health (NIH) [NIH CA109335, NIH CA122105, P01 CA34233]
- Dwoskin Family Foundations
- FEDER
- MICINN [SAF2009-08803, SAF2012-32810]
- Junta de Castilla y Leon [CSI007A11-2]
- Junta de Castilla y Leon (Proyecto Biomedicina)
- MEC OncoBIO Consolider-Ingenio [CSD2007-0017]
- Sandra Ibarra Foundation
- Group of Excellence from Junta de Castilla y Leon [GR15]
- ARIMMORA project (FP7-ENV, European Union Seventh Framework Programme))
- Proyecto en Red de Investigacion en Celulas Madre Tumorales en Cancer de Mama
- Obra Social Kutxa y Conserjeria de Sanidad de la Junta de Castilla y Leon
The human germinal centre-associated lymphoma gene is specifically expressed in germinal centre B-lymphocytes and germinal centre-derived B-cell lymphomas, but its function is largely unknown. Here we demonstrate that human germinal centre-associated lymphoma directly binds to Syk in B cells, increases its kinase activity on B-cell receptor stimulation and leads to enhanced activation of Syk downstream effectors. To further investigate these findings in vivo, human germinal centre-associated lymphoma transgenic mice were generated. Starting from 12 months of age these mice developed polyclonal B-cell lymphoid hyperplasia, hypergammaglobulinemia and systemic reactive amyloid A ( AA) amyloidosis, leading to shortened survival. The lymphoid hyperplasia in the human germinal centre-associated lymphoma transgenic mice are likely attributable to enhanced B-cell receptor signalling as shown by increased Syk phosphorylation, ex vivo B-cell proliferation and increased RhoA activation. Overall, our study shows for the first time that the germinal centre protein human germinal centre-associated lymphoma regulates B-cell receptor signalling in B-lymphocytes which, without appropriate control, may lead to B-cell lymphoproliferation.
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