The Fms-like tyrosine kinase 3 ligand, a mediator of B cell survival, is also a marker of lymphoma in primary Sjögren's syndrome. - Archive ouverte HAL
Article Dans Une Revue Arthritis and Rheumatism Année : 2010

The Fms-like tyrosine kinase 3 ligand, a mediator of B cell survival, is also a marker of lymphoma in primary Sjögren's syndrome.

Résumé

To determine if the Fms-like tyrosine kinase 3 ligand (Flt-3L), a cytokine implicated in B cell ontogenesis and proliferation in hematologic malignancies, might be responsible for the increased numbers of circulating Bm2 and Bm2′ B cell subsets in patients with primary Sjögren's syndrome (SS). Serum levels of Flt-3L were measured in 64 patients with primary SS and in 20 healthy controls matched for age and sex. Flt-3L and its receptor Flt-3 were quantified in circulating B cells and in salivary gland (SG) biopsy tissues by immunofluorescence analysis. The effect of Flt-3L on circulating B lymphocytes was then determined by coculture with cells of a human SG (HSG) epithelial cell line. Serum levels of Flt-3L were increased in patients with primary SS as compared with controls (mean ± SD 135.8 ± 5.5 versus 64.4 ± 4.5 pg/ml; P < 0.001). Serum levels of Flt-3L in primary SS patients correlated with the numbers of Bm2 and Bm2′ cells (r = 0.46, P < 0.0006), and Flt-3 was selectively expressed in Bm2 and Bm2′ cells. B cell culture experiments showed that Flt-3L potentiated the proliferative effect of anti-IgM stimulation. In SGs, we found that infiltrating B cells expressed Flt-3 and epithelial cells produced Flt-3L. Finally, Flt-3L levels were associated with high disease activity scores and increased risk of developing lymphoma. Serum levels of Flt-3L are elevated in patients with primary SS and correlate with abnormal B cell distribution. Flt-3 is mainly expressed by Bm2 and Bm2′ cells. Serum levels of Flt-3L might explain the clinical evolution of primary SS to B cell lymphoma that is observed in some patients, thus opening the possibility of new avenues for therapy.

Domaines

Immunologie
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Dates et versions

hal-01150521 , version 1 (11-05-2015)

Identifiants

  • HAL Id : hal-01150521 , version 1
  • PUBMED : 20556820

Citer

Gabriel J Tobón, Yves Renaudineau, Sophie Hillion, Divi Cornec, Valérie Devauchelle-Pensec, et al.. The Fms-like tyrosine kinase 3 ligand, a mediator of B cell survival, is also a marker of lymphoma in primary Sjögren's syndrome.. Arthritis and Rheumatism, 2010, 62 (11), pp.3447-56. ⟨hal-01150521⟩

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