近期《自然—免疫學(xué)》上的一項(xiàng)研究為我們揭示了小鼠身體是如何限制IgA抗體在血液循環(huán)中的數(shù)量，從而降低腎臟患病風(fēng)險(xiǎn)的,。這或許有助于為那些受到IgA調(diào)控下的自體免疫折磨的患者開發(fā)新的干預(yù)療法,。
Shao-Cong Sun等人對(duì)產(chǎn)生抗體的細(xì)胞——B免疫細(xì)胞進(jìn)行了研究。B細(xì)胞的活躍能夠增加抗體產(chǎn)量并引發(fā)免疫球蛋白類別轉(zhuǎn)換過程,，從而決定抗體的最終類型,。研究人員發(fā)現(xiàn)一種名為TBK1的調(diào)節(jié)分子能夠阻止向IgA的轉(zhuǎn)變。一旦小鼠的B細(xì)胞缺乏TBK1表達(dá),，其體內(nèi)血清會(huì)產(chǎn)生更大量的IgA,，包括可針對(duì)自身組織的抗體。隨著自體免疫IgA復(fù)合物在腎臟中的積累,，小鼠會(huì)產(chǎn)生腎功能障礙以及與IgA有關(guān)的人類患病癥狀,。（生物谷Bioon.com）
doi: 10.1038/ni.2423
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The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling
Jin J, Xiao Y, Chang JH, Yu J, Hu H, Starr R, Brittain GC, Chang M, Cheng X, Sun SC.
Immunoglobulin class switching is crucial for the generation of antibody diversity in humoral immunity and, when deregulated, also has severe pathological consequences. How the magnitude of immunoglobulin isotype switching is controlled is still poorly understood. Here we identify the kinase TBK1 as a pivotal negative regulator of class switching to the immunoglobulin A (IgA) isotype. B cell-specific ablation of TBK1 in mice resulted in uncontrolled production of IgA and the development of nephropathy-like disease signs. TBK1 negatively regulated IgA class switching by attenuating noncanonical signaling via the transcription factor NF-κB, an action that involved TBK1-mediated phosphorylation and subsequent degradation of the NF-κB-inducing kinase NIK. Our findings establish TBK1 as a pivotal negative regulator of the noncanonical NF-κB pathway and identify a unique mechanism that controls IgA production
