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

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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

Fingerprint

Germinal Center
Amyloidosis
Hyperplasia
B-Lymphocytes
Chemical activation
Cells
activation
proteins
Proteins
Lymphoma
Lymphocytes
mice
lymphocytes
Transgenic Mice
Phosphorylation
effectors
Cell proliferation
phosphorylation
Hypergammaglobulinemia
Amyloid

ASJC Scopus subject areas

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

Cite this

Romero-Camarero, I., Jiang, X., Natkunam, Y., Lu, X., Vicente-Dueñas, C., Gonzalez-Herrero, I., ... 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

Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation. / Romero-Camarero, Isabel; Jiang, Xiaoyu; Natkunam, Yasodha; Lu, Xiaoqing; Vicente-Dueñas, Carolina; Gonzalez-Herrero, Ines; Flores, Teresa; Garcia, Juan Luis; McNamara, George; Kunder, Christian; Zhao, Shuchun; Segura, Victor; Fontan, Lorena; Martínez-Climent, Jose A.; García-Criado, Francisco Javier; Theis, Jason D.; Dogan, Ahmet; Campos-Sánchez, Elena; Green, Michael R.; Alizadeh, Ash A.; Cobaleda, Cesar; Sánchez-García, Isidro; Lossos, Izidore S.

In: Nature Communications, Vol. 4, 1338, 2013.

Research output: Contribution to journalArticle

Romero-Camarero, I, Jiang, X, Natkunam, Y, Lu, X, Vicente-Dueñas, C, Gonzalez-Herrero, I, Flores, T, Garcia, JL, McNamara, G, Kunder, C, Zhao, S, Segura, V, Fontan, L, Martínez-Climent, JA, García-Criado, FJ, Theis, JD, Dogan, A, Campos-Sánchez, E, Green, MR, Alizadeh, AA, Cobaleda, C, Sánchez-García, I & Lossos, IS 2013, 'Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation', Nature Communications, vol. 4, 1338. https://doi.org/10.1038/ncomms2334
Romero-Camarero I, Jiang X, Natkunam Y, Lu X, Vicente-Dueñas C, Gonzalez-Herrero I et al. Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation. Nature Communications. 2013;4. 1338. https://doi.org/10.1038/ncomms2334
Romero-Camarero, Isabel ; Jiang, Xiaoyu ; Natkunam, Yasodha ; Lu, Xiaoqing ; Vicente-Dueñas, Carolina ; Gonzalez-Herrero, Ines ; Flores, Teresa ; Garcia, Juan Luis ; McNamara, George ; Kunder, Christian ; Zhao, Shuchun ; Segura, Victor ; Fontan, Lorena ; Martínez-Climent, Jose A. ; García-Criado, Francisco Javier ; Theis, Jason D. ; Dogan, Ahmet ; Campos-Sánchez, Elena ; Green, Michael R. ; Alizadeh, Ash A. ; Cobaleda, Cesar ; Sánchez-García, Isidro ; Lossos, Izidore S. / Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation. In: Nature Communications. 2013 ; Vol. 4.
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