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Title

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

AuthorsRomero-Camarero, Isabel ; Jiang, Xingyu ; Vicente-Dueñas, Carolina ; González-Herrero, Inés ; Flores, Teresa; García, Juan L. ; Segura, Víctor; Fontán, Lorena; Martínez-Climent, José Ángel; García-Criado, Francisco Javier; Campos-Sánchez, Elena ; Cobaleda, César ; Sánchez García, Isidro ; Lossos, Izidore S.
Issue Date2013
PublisherNature Publishing Group
CitationNature Communications 4: 1338 (2013)
AbstractThe 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.
DescriptionPMCID: PMC3545406.-- et al.
Publisher version (URL)http://dx.doi.org/10.1038/ncomms2334
URIhttp://hdl.handle.net/10261/97641
DOI10.1038/ncomms2334
ISSN2041-1723
Identifiersissn: 2041-1723
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