Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation.
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Romero-Camarero I, Jiang X, Natkunam Y, Lu X, Vicente-Duenas C, Gonzalez-Herrero I, Flores T, Garcia JL, McNamara G, Kunder C, Zhao S, Segura V, Fontan L, Martinez-Climent JA, Garcia-Criado FJ, Theis JD, Dogan A, Campos-Sanchez E, Green MR, Alizadeh AA, Cobaleda C, Sanchez-Garcia I, Lossos IS
Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation.
Nat Commun. 2013;4:1338. doi: 10.1038/ncomms2334.
- PubMed ID
- 23299888 [ View in PubMed]
- 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.