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Abstract
Although the aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. Here we show that an unusual CD11chiT-bet+ B cell subset, with a unique expression profile including chemokine receptors consistent with migration to target tissues, is expanded in SLE patients, present in nephrotic kidney, enriched for autoreactive specificities and correlates with defined clinical manifestations. IL-21 can potently induce CD11chiT-bet+ B cells and promote the differentiation of these cells into Ig-secreting autoreactive plasma cells. While murine studies have identified a role for T-bet-expressing B cells in autoimmunity, this study describes and exemplifies the importance of CD11chiT-bet+ B cells in human SLE.
Highlights
The aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated
A high proportion of circulating B cells isolated from Systemic lupus erythematosus (SLE) patients displayed greatly increased density of CD11c, comparable to the density observed on dendritic cells isolated from the same individual (Fig. 1a)
CD11chi B cells were found at the highest frequencies in SLE patients with coincident active nephritis and malar rash (Fig. 1d), suggesting that this B cell subset has the potential to associate with specific clinical disease manifestations
Summary
The aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. In SLE, Sanz and colleagues report a population of autoreactive memory B cells that lacks CD27 expression and is associated with clinical manifestations of lupus[5]. Other B cell populations are described in SLE including CD19hiCXCR3hi B cells that associate with poor clinical outcomes after rituximab treatment[8], or CD24−-activated naive B cells that may be precursors of plasma cells[9] Another population of B cells described to be increased in autoimmune disease is a B cell subset that expresses CD11c, a marker traditionally associated with dendritic cells. Removal of CD11c+ B cells from mice immunised with TLR7 agonist markedly reduces anti-Smith (Sm) titres[11] Taken together, these studies suggest that in pre-clinical murine models, the majority of B cells with autoreactive specificity originate from CD11c+T-bet+ B cells. Neither T-bet expression in B cells from SLE patients, nor the potential contribution of these cells to disease manifestations has been systematically investigated
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