IL-7 modulates B cells survival and activation by inducing BAFF and CD70 expression in T cells
- 作者：Stefano Sammicheli ; Nicolas Ruffin ; Rebecka Lantto ; Nancy Vivar ; Francesca Chiodi ; Bence Rethi ; Bence.Rethi@ki.se
- 关键词：Interleukin-7 ; CD70 ; BAFF ; B cell activation ; B cell apoptosis
- 刊名：Journal of Autoimmunity
- 出版年：2012
- 期刊代码：101_08968411
- 类别：imm
- 出版时间：June, 2012
- 卷：38
- 期：4
- 页码：304-314
- 文件大小：1223 K
摘要
Interleukin-7 (IL-7) promotes the maintenance and activation of peripheral T cells, whereas it does not act directly on mature B cells due to the lack of IL-7R伪 expression on these. We report here that, in spite of the insensitivity of B cells to IL-7, high concentration of IL-7 can lead to increased B cell survival and antibody production in the presence of T cells, without the use of any further B cell stimulatory signal. IL-7 promoted B cell activation through inducing CD70 expression on resting T cells, particularly on CD4+ memory cells. The interaction of CD70 molecules with the B cell costimulatory receptor CD27 led to B cell proliferation, the accumulation of CD38聽+聽CD20- plasmablasts and antibody production. In addition, IL-7 treatment induced BAFF secretion from resting peripheral T cells thereby promoting B cell survival. IL-7 levels can increase in lymphopenic conditions, in autoimmune diseases or in patients receiving T cell regenerative IL-7 therapy. Based on our findings high IL-7 levels can lead to increased B cell activation by inducing the B cell regulatory proteins CD70 and BAFF in resting T cells. Such activity might be beneficial in short term immune-stimulatory IL-7 therapies; permanently increased IL-7 levels, on the other hand, can contribute to impaired B cell tolerance.