The IgM receptor FcμR limits tonic BCR signaling by regulating expression of the IgM BCR.
The IgM receptor FcμR limits tonic BCR signaling by regulating expression of the IgM BCR.
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DOI：
10.1038/ni.3677
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发表时间：
2017-03
影响因子：
30.5
通讯作者：
Baumgarth N
中科院分区：
文献类型：
--
作者：
Nguyen TT;Kläsener K;Zürn C;Castillo PA;Brust-Mascher I;Imai DM;Bevins CL;Reardon C;Reth M;Baumgarth N
IgM Fc受体（FcμR）最初克隆为“Fas-凋亡抑制分子（FAIM 3/TOSO）”，可作为多种细胞类型上分泌IgM的细胞表面受体。我们报告FcμR也在发育中的B细胞的trans-Golgi网络中表达，在那里它限制IgM-而不是IgD-BCR转运。在FcμR缺失的情况下，IgM-BCR表面表达增加，导致增强的强直性BCR信号传导。B细胞特异性Fcμ R缺乏增强了B-1细胞的自发分化，导致天然IgM水平升高，以及B-2细胞稳态失调，导致自发性生发中心形成、血清自身抗体滴度升高和B细胞过度蓄积。因此，FcμR/FAIM 3是B细胞生物学的关键调节因子，通过限制IgM-BCR转运和细胞表面表达。
The IgM Fc receptor (FcμR), originally cloned as “Fas-apoptosis inhibitory molecule (FAIM3/TOSO)” can function as a cell surface receptor for secreted IgM on a variety of cell types. We report that FcμR also is expressed in the trans-Golgi network of developing B cells, where it constrains IgM- but not IgD-BCR transport. In FcμR absence, IgM-BCR surface expression was increased, resulting in enhanced tonic BCR signaling. B cell-specific FcμR-deficiency enhanced spontaneous differentiation of B-1 cells, resulting in increases in natural IgM levels, and dysregulated B-2 cell homeostasis, causing spontaneous germinal center formation, increased serum autoantibody titers, and excessive B cell accumulation. Thus, FcμR/FAIM3 is a critical regulator of B cell biology by constraining IgM-BCR transport and cell surface expression.