Nature Communications (2013) 4:1338 doi: 10.1038/ncomms2334. PMID: 23299888


Isabel Romero Camarero, Xiaoyu Jiang, Yasodha Natkunam, Xiaoqing Lu, Carolina Vicente Dueñas, Ines González Herrero, Teresa Flores, Juan Luis García, George McNamara, Christian Kunder, Shuchun Zhao, Víctor Segura, Lorena Fontán , Jose A. Martínez Climent, Francisco Javier García Criado, Jason D. Theis, Ahmet Dogan, Elena Campos Sánchez, Michael R. Green, Ash A. Alizadeh, César Cobaleda, Isidro Sánchez García, Izidore S. Lossos.


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.


HGAL, de las siglas Human Germinal Center Associated Lymphoma es un gen novedoso que fue descrito por primera vez en el año 2003 y, desde entonces, ha sido relacionado con la supervivencia de pacientes con linfoma B difuso de célula grande y linfoma Hodgkin, pero no se conocía su función biológica. Los resultados publicados en Nature Communications, demuestran, que, la expresión no controlada de HGAL produce una hiperplasia linfoide B. El mecanismo molecular que utiliza HGAL está mediado por la activación de la tirosín-quinasa SyK, que altera la señalización del receptor de los linfocitos B. Estos hallazgos sugieren que los inhibidores de SyK podrían llegar a ser útiles en el tratamiento de esta enfermedad.

imagen julio


El trabajo publicado ha sido posible gracias a la colaboración de los grupos del Dr. Izidore Lossos, en la Universidad de Miami e Isidro Sánchez García, del Instituto de Biología Molecular y Celular del Cáncer de Salamanca. El Dr. Lossos fue uno de los descubridores de HGAL, y la investigación desarrollada en su laboratorio se centra en los genes y mecanismos de patogénesis de linfomas humanos. El grupo del Dr. Sánchez García trabaja en entender los mecanismos moleculares que gobiernan la génesis y mantenimiento de las células stem cancerígenas para el desarrollo de nuevos tratamientos frente al cáncer.

Para ver el artículo completo, pulse aqui

Más artículos en la revista SEBBM.

Did you publish an interesting article recently?

Send it through our application form and we will contact you. Age limit: 32.

The selected articles will participate at the Award to the best article of young people of the SEBBM which will be given during SEBBM conference, that will take place at Spain (free registration, travel and accommodation).

More articles of the month

Antigen retrieval and clearing for whole-organ immunofluorescence by FLASH


Advances in light-sheet and confocal microscopy now allow imaging of cleared large biological tissue samples and enable the 3D appreciation of cell and protein localization in their native organ environment...

Read more

Viral Bcl2s' transmembrane domain interact with host Bcl2 proteins to control cellular apoptosis


Viral control of programmed cell death relies in part on the expression of viral analogs of the B-cell lymphoma 2 (Bcl2) protein known as viral Bcl2s (vBcl2s). vBcl2s control apoptosis...

Read more

Macrophages promote endothelial-to-mesenchymal transition via MT1-MMP/TGFß after myocardial infarction


Macrophages (Mφs) produce factors that participate in cardiac repair and remodeling after myocardial infarction (MI); however, how these factors crosstalk with other cell types mediating repair is not fully understood...

Read more

Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics


Heteroplasmy, multiple variants of mitochondrial DNA (mtDNA) in the same cytoplasm, may be naturally generated by mutations but is counteracted by a genetic mtDNA bottleneck during oocyte development. Engineered heteroplasmic...

Read more

Mechanisms of autoregulation of C3G, activator of the GTPase Rap1, and its catalytic deregulation in lymphomas


C3G is a guanine nucleotide exchange factor (GEF) that regulates cell adhesion and migration by activating the GTPase Rap1. The GEF activity of C3G is stimulated by the adaptor proteins...

Read more

Expression of the long non-coding RNA TCL6 is associated with clinical outcome in pediatric B-cell acute lymphoblastic leukemia


The reciprocal translocation t(12;21)(p13;q22)[ETV6/RUNX1] is the most frequent chromosomal rearrangement in pediatric B-cell acute lymphoblastic leukemia(B-ALL). Long non-coding RNAs (lncRNAs) play important roles in numerous diseases and they represent an...

Read more

Evaluation of different approaches used to study membrane permeabilization by actinoporins on model lipid vesicles


Release of aqueous contents from model lipid vesicles has been a standard procedure to evaluate pore formation efficiency by actinoporins, such as sticholysin II (StnII), for the last few decades...

Read more

ADAR1-mediated RNA editing is a novel oncogenic process in thyroid cancer and regulates miR-200 activity


Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA. A-to-I editing of RNA is a widespread posttranscriptional process that has recently emerged as an important mechanism...

Read more

Sarcoplasmic reticulum Ca2+ decreases with age and correlates with the decline in muscle function in Drosophila


Sarcopenia, the loss of muscle mass and strength associated with age, has been linked to impairment of the cytosolic Ca2+ peak that triggers muscle contraction, but mechanistic details remain unknown...

Read more

Structural basis for substrate specificity and catalysis of α1,6-fucosyltransferase


Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans. A single human enzyme α1,6-fucosyltransferase (FUT8) is the...

Read more

Protector Members