Aberrant expression of BAFF by B lymphocytes infiltrating the salivary glands of patients with primary Sjögren's syndrome

Daridon, Capucine; Devauchelle, Valérie; Hutin, P.; Berre, Rozenn Le; Martins-Carvalho, C.; Bendaoud, Boutahar; Dueymes, Maryvonne; Saraux, Alain; Youinou, Pierre; Pers, Jacques‐Olivier

doi:10.1002/art.22458

Cited by 189 publications

(110 citation statements)

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“…This is caused by amplification of the BAFF gene in human B cells (39). We have demonstrated aberrant expression of BAFF, not only in activated T lymphocytes as expected (30) (Figure 3), but also in B lymphocytes infiltrating the salivary glands of patients with SS (40). There is also in vitro and in vivo evidence that activation of B cells induces BAFF and APRIL expression in B cells from normal and SLEprone mice.…”

Section: B Cell-modulating Factors In Autoimmunitysupporting

confidence: 60%

B lymphocyte cytokines and rheumatic autoimmune disease

Youinou¹,

Taher²,

Pers³

et al. 2009

Arthritis & Rheumatism

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Section: B Cell-modulating Factors In Autoimmunitysupporting

confidence: 60%

B lymphocyte cytokines and rheumatic autoimmune disease

Youinou¹,

Taher²,

Pers³

et al. 2009

Arthritis & Rheumatism

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“…In human Sjö gren's syndrome, immunohistochemical evidence for BLyS production in epithelial cells of salivary glands exists. 28,36 BLySpositive monocytes, 37 B, 38 and T 37 lymphocytes as well as BAFF-R-positive B lymphocytes 38 infiltrating salivary glands in Sjö gren's syndrome have been demonstrated, similar to the BLyS-/BAFF-R-positive interstitial cell infiltrate seen in lupus nephritis. In human rheumatoid arthritis, different cells seem to express the B-cell survival factors: one immunohistochemical study found APRIL in germinal center positive synovitis in CD83-positive dendritic cells, whereas BLyS was derived from CD68-positive monocytes/macrophages.…”

Section: Discussionmentioning

confidence: 65%

Intrarenal production of B-cell survival factors in human lupus nephritis

et al. 2011

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The B-cell survival factors APRIL and BLyS are important for B-cell maturation and activation and contribute to human autoimmune diseases. Interference with B-cell function by targeting these molecules is currently being investigated in large clinical trials for systemic lupus erythematosus. The local expression patterns of APRIL and BLyS have not been investigated in detail in kidneys with lupus nephritis. We studied the mRNA expression of APRIL, BLyS, and the corresponding receptors BCMA, TACI, and BAFF-R in microdissected human biopsies with proliferative lupus nephritis (n ¼ 25) and compared it with pretransplant biopsies of living donors (n ¼ 9). APRIL and BLyS mRNA levels were significantly higher in glomeruli of patients with proliferative lupus nephritis (12-and 30-fold, respectively). Tubulointerstitial expression of APRIL, BLyS, BCMA, and TACI was also significantly elevated. To localize the respective proteins in the kidney, APRIL, BLyS, and BAFF-R were studied by immunohistochemistry in renal biopsies with proliferative (n ¼ 21) or membranous (n ¼ 8) lupus nephritis. APRIL was prominently expressed in glomeruli with proliferative, but not membranous, lupus nephritis. The staining pattern was consistent with mesangial cells. A prominent accumulation of CD68-positive cells was present in glomeruli in association with APRIL expression. APRIL, BLyS, and BAFF-R were also expressed in interstitial inflammatory cell accumulation. This is the first study, which details local expression of APRIL and BLyS in glomeruli and tubulointerstitium of human proliferative lupus nephritis. This information might help define intrarenal effects of APRIL and BLyS inhibition in human lupus nephritis.

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“…Though BAFF originally was thought to be specifically expressed in cells only of the myeloid lineage (17)(18)(19), it has more recently been shown that ac-tivated B cells express both BAFF and APRIL, in T cell-dependent and independent ways (20)(21)(22)(23)(24). Indeed, in patients with SLE even T cells express abundant BAFF, in particular when they are activated (25).…”

Section: Discussionmentioning

confidence: 99%