LKB1 inhibition of NF-κB in B cells prevents T follicular helper cell differentiation and germinal center formation
LKB1 inhibition of NF-κB in B cells prevents T follicular helper cell differentiation and germinal center formation
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DOI：
10.15252/embr.201439505
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发表时间：
2015-06-01
期刊：
影响因子：
7.7
通讯作者：
Teitell, Michael A.
中科院分区：
文献类型：
--
作者：
Walsh, Nicole C.;Waters, Lynnea R.;Teitell, Michael A.
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-kappa B, which is suppressed by active LKB1. Secreted IL-6 drives T-cell activation and IL-21 production, promoting T follicular helper (T-FH) cell differentiation and expansion to support a similar to 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 T-FH-cell differentiation and expansion. Together, these data reveal cell intrinsic and surprising cell extrinsic roles for LKB1 in B cells that control T-FH-cell differentiation and GC formation, and place LKB1 as a central regulator of T-cell-dependent humoral immunity.
