Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
Eur J Immunol. 2015 Apr;45(4):1228-37. doi: 10.1002/eji.201444917. Epub 2015 Jan 22.
Selection of the primary antibody repertoire takes place in pro-/pre-B cells, and subsequently in immature and transitional B cells. At the first checkpoint, μ heavy (μH) chains assemble with surrogate light (SL) chain into a precursor B-cell receptor. In mice lacking SL chain, μH chain selection is impaired, and serum autoantibody levels are elevated. However, whether the development of autoantibody-producing cells is due to an inability of the resultant B-cell receptors to induce central and/or peripheral B-cell tolerance or other factors is unknown. Here, we show that receptor editing is defective, and that a higher proportion of BM immature B cells are prone to undergoing apoptosis. Furthermore, transitional B cells are also more prone to undergoing apoptosis, with a stronger selection pressure to enter the follicular B-cell pool. Those that enter the marginal zone (MZ) B-cell pool escape selection and survive, possibly due to the B-lymphopenia and elevated levels of B-cell activating factor. Moreover, the MZ B cells are responsible for the elevated IgM anti-dsDNA antibody levels detected in these mice. Thus, the SL chain is required for central and peripheral B-cell tolerance and inhibits anti-DNA antibody production by MZ B cells.
在祖/前 B 细胞中发生主要抗体库的选择，随后在未成熟和过渡 B 细胞中发生选择。在缺乏 SL 链的小鼠中，μ 重（μH）链与替代轻（SL）链组装成前 B 细胞受体。在这些小鼠中，μH 链选择受损，血清自身抗体水平升高。然而，产生自身抗体的细胞的发育是由于所得 B 细胞受体不能诱导中枢和/或外周 B 细胞耐受，还是由于其他因素尚不清楚。在这里，我们表明受体编辑有缺陷，并且更多比例的 BM 未成熟 B 细胞容易发生凋亡。此外，过渡 B 细胞也更容易发生凋亡，进入滤泡 B 细胞池的选择压力更强。那些进入边缘区（MZ）B 细胞池的细胞逃避选择并存活下来，这可能是由于 B 淋巴细胞减少症和 B 细胞激活因子水平升高所致。此外，MZ B 细胞负责检测到这些小鼠中升高的 IgM 抗 dsDNA 抗体水平。因此，SL 链是中枢和外周 B 细胞耐受所必需的，并抑制 MZ B 细胞产生抗 DNA 抗体。
