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

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. AlizadehCesar Cobaleda, Isidro Sánchez-García, Izidore S. Lossos

Research output: Contribution to journalArticle

32 Scopus citations

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.

Original languageEnglish (US)
Article number1338
JournalNature communications
Volume4
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Romero-Camarero, I., Jiang, X., Natkunam, Y., Lu, X., Vicente-Dueñas, C., Gonzalez-Herrero, I., Flores, T., Garcia, J. L., McNamara, G., Kunder, C., Zhao, S., Segura, V., Fontan, L., Martínez-Climent, J. A., García-Criado, F. J., Theis, J. D., Dogan, A., Campos-Sánchez, E., Green, M. R., ... Lossos, I. S. (2013). Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation. Nature communications, 4, [1338]. https://doi.org/10.1038/ncomms2334