Generation of functional murine CD11c+ age‐associated B cells in the absence of B cell T‐bet expression,European Journal of Immunology

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Generation of functional murine CD11c+ age‐associated B cells in the absence of B cell T‐bet expression
European Journal of Immunology ( IF 4.5 ) Pub Date : 2018-11-05 , DOI: 10.1002/eji.201847641
Samuel W. Du ₁ , Tanvi Arkatkar ₁ , Holly M. Jacobs ₁ , David J. Rawlings _{1,

2,

3} , Shaun W. Jackson _{1,

3}

Affiliation

Age‐associated B cells (ABC), a novel subset of activated B cells defined by CD11b and CD11c expression, have been linked with both protective anti‐viral responses and the pathogenesis of systemic autoimmunity. Expression of the T_H1 lineage transcription factor T‐bet has been identified as a defining feature of ABC biology, with B cell‐intrinsic expression of this transcription factor proposed to be required for ABC formation. In contrast to this model, we report that Tbx21 (encoding T‐bet)‐deficient B cells upregulate CD11b and CD11c surface expression in vitro in response to integrated TLR and cytokine signals. Moreover, B cell‐intrinsic T‐bet deletion in a murine lupus model exerted no impact of ABC generation in vivo, with Tbx21^−/− ABCs exhibiting an identical surface phenotype to wild‐type (WT) ABCs. Importantly, WT and Tbx21^−/− ABCs sorted from autoimmune mice produced equivalent amounts of IgM and IgG ex vivo following TLR stimulation, indicating that T‐bet‐deficient ABCs are likely functional in vivo. In summary, our data contradict the established literature by demonstrating that T‐bet expression is not uniformly required for ABC generation.

中文翻译：

在没有B细胞T-bet表达的情况下生成功能性鼠CD11c +与年龄相关的B细胞

与年龄相关的B细胞（ABC）是由CD11b和CD11c表达定义的活化B细胞的一个新子集，已与保护性抗病毒应答和全身性自身免疫性疾病的发病机制联系在一起。T _H 1谱系转录因子T-bet的表达已被确定为ABC生物学的定义特征，该转录因子的B细胞内在表达被认为是ABC形成所必需的。与该模型相反，我们报告说，响应整合的TLR和细胞因子信号，Tbx21（编码T-bet）缺陷的B细胞在体外上调CD11b和CD11c表面表达。此外，在鼠狼疮模型中，B细胞内在性T-bet缺失对体内ABC产生没有影响，Tbx21 ^-/-表现出与野生型（WT）相同的表面表型的ABC。重要的是，从自身免疫小鼠中分选出的WT和Tbx21 ^-/- ABC在TLR刺激后离体产生了等量的IgM和IgG，这表明缺乏T-bet的ABC可能在体内起作用。总而言之，我们的数据通过证明T-bet表达并不是ABC生成统一需要的，因而与已有文献相矛盾。

更新日期：2018-11-05

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