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题目:: LKB1 inhibition of NF-κB in B cells prevents T follicular helper cell differentiation and germinal center formation.
作者:: Walsh(Nicole C),Waters(Lynnea R),Fowler(Jessica A),Lin(Mark),Cunningham(Cameron R),Brooks(David G),Rehg(Jerold E),Morse(Herbert C),Teitell(Michael A)
状态:: 发布时间2015-06-04 , 更新时间 2016-11-04
期刊:: EMBO Rep
摘要:: T-cell-dependent antigenic stimulation drives the differentiation of B cells into antibody-secreting plasma cells and memory B cells, but how B cells regulate this process is unclear. We show that LKB1 expression in B cells maintains B-cell quiescence and prevents the premature formation of germinal centers (GCs). Lkb1-deficient B cells (BKO) undergo spontaneous B-cell activation and secretion of multiple inflammatory cytokines, which leads to splenomegaly caused by an unexpected expansion of T cells. Within this cytokine response, increased IL-6 production results from heightened activation of NF-κB, which is suppressed by active LKB1. Secreted IL-6 drives T-cell activation and IL-21 production, promoting T follicular helper (TFH ) cell differentiation and expansion to support a ~100-fold increase in steady-state GC B cells. Blockade of IL-6 secretion by BKO B cells inhibits IL-21 expression, a known inducer of TFH -cell differentiation and expansion. Together, these data reveal cell intrinsic and surprising cell extrinsic roles for LKB1 in B cells that control TFH -cell differentiation and GC formation, and place LKB1 as a central regulator of T-cell-dependent humoral immunity.
语言:: eng
DOI:

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