Document Detail


Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation.
MedLine Citation:
PMID:  23299888     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
22920938 - Nvp-bez235 alone and in combination in mantle cell lymphoma: an effective therapeutic s...
23419678 - Mesenchymal stromal cell supported umbilical cord blood ex vivo expansion enhances regu...
23300748 - Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therap...
23717378 - Correction: curcumin inhibits cd4(+) t cell activation, but augments cd69 expression an...
1355318 - Development of the b- and t-cell compartments in porcine lymphoid organs from birth to ...
21418508 - Age-related changes in human hematopoietic stem/progenitor cells.
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nature communications     Volume:  4     ISSN:  2041-1723     ISO Abbreviation:  Nat Commun     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-09     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101528555     Medline TA:  Nat Commun     Country:  England    
Other Details:
Languages:  eng     Pagination:  1338     Citation Subset:  IM    
Affiliation:
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].
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Extensive diversification of IgH subclass-encoding genes and IgM subclass switching in crocodilians.
Next Document:  Probing the electronic structure at semiconductor surfaces using charge transport in nanomembranes.