| Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation. | |
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MedLine Citation:
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PMID: 23299888 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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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Authors:
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Isabel Romero-Camarero; Xiaoyu Jiang; Yasodha Natkunam; Xiaoqing Lu; Carolina Vicente-Dueñas; Ines Gonzalez-Herrero; Teresa Flores; Juan Luis Garcia; George McNamara; Christian Kunder; Shuchun Zhao; Victor Segura; Lorena Fontan; Jose A Martínez-Climent; Francisco Javier García-Criado; Jason D Theis; Ahmet Dogan; Elena Campos-Sánchez; Michael R Green; Ash A Alizadeh; Cesar Cobaleda; Isidro Sánchez-García; Izidore S Lossos |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Nature communications Volume: 4 ISSN: 2041-1723 ISO Abbreviation: Nat Commun Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-01-09 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101528555 Medline TA: Nat Commun Country: England |
Other Details:
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Languages: eng Pagination: 1338 Citation Subset: IM |
Affiliation:
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1] Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, 37007 Salamanca, Spain [2] Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain [3]. |
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