2. Academic Validation
  3. Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation

Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation

  • Nat Commun. 2013;4:1338. doi: 10.1038/ncomms2334.
Isabel Romero-Camarero 1,  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
Affiliations

Affiliation

  • 1 Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, 37007 Salamanca, Spain.
PMID: 23299888 DOI: 10.1038/ncomms2334
Abstract

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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