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IgM and IgD B cell receptors differentially respond to endogenous antigens and control B cell fate
eLife ( IF 6.4 ) Pub Date : 2018-03-09 , DOI: 10.7554/elife.35074
Mark Noviski 1 , James L Mueller 2 , Anne Satterthwaite 3 , Lee Ann Garrett-Sinha 4 , Frank Brombacher 5, 6 , Julie Zikherman 2
Affiliation  

Naive B cells co-express two BCR isotypes, IgM and IgD, with identical antigen-binding domains but distinct constant regions. IgM but not IgD is downregulated on autoreactive B cells. Because these isotypes are presumed to be redundant, it is unknown how this could impose tolerance. We introduced the Nur77-eGFP reporter of BCR signaling into mice that express each BCR isotype alone. Despite signaling strongly in vitro, IgD is less sensitive than IgM to endogenous antigen in vivo and developmental fate decisions are skewed accordingly. IgD-only Lyn−/− B cells cannot generate autoantibodies and short-lived plasma cells (SLPCs) in vivo, a fate thought to be driven by intense BCR signaling induced by endogenous antigens. Similarly, IgD-only B cells generate normal germinal center, but impaired IgG1+ SLPC responses to T-dependent immunization. We propose a role for IgD in maintaining the quiescence of autoreactive B cells and restricting their differentiation into autoantibody secreting cells.

中文翻译:

IgM 和 IgD B 细胞受体对内源性抗原的反应不同并控制 B 细胞命运

幼稚 B 细胞共表达两种 BCR 同种型,IgM 和 IgD,具有相同的抗原结合域但不同的恒定区。IgM 但不是 IgD 在自身反应性 B 细胞上被下调。因为假定这些同种型是多余的,所以不知道这如何产生耐受性。我们将 BCR 信号的 Nur77-eGFP 报告基因引入单独表达每个 BCR 同种型的小鼠。尽管在体外信号强烈,但 IgD 对体内内源性抗原的敏感性不如 IgM,因此发育命运决定会发生偏差。仅 IgD 的 Lyn-/- B 细胞不能在体内产生自身抗体和短寿命浆细胞 (SLPC),这种命运被认为是由内源性抗原诱导的强烈 BCR 信号驱动的。同样,仅 IgD 的 B 细胞产生正常的生发中心,但会削弱 IgG1+ SLPC 对 T 依赖性免疫的反应。
更新日期:2018-03-09
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