Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, Novy Hradek, Czech Republic.
Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, Novy Hradek, Czech Republic.
Dev Comp Immunol. 2020 Oct;111:103751. doi: 10.1016/j.dci.2020.103751. Epub 2020 May 23.
Developmental pathways for B cell lymphogenesis are sufficiently known only in mice and humans. However, both of these species rearrange immunoglobulin heavy chains (IgH) before light chains (IgL) while IgL precedes IgH rearrangement in swine. We demonstrate here that this reversed order of rearrangements have some concealed consequences: (1) we confirmed that although IgLκ rearrangement is initial, most IgLλ B cells are generated earlier and before IgH rearrangements, while most IgLκ B cells later and after IgH rearrangements, (2) the second IgLκ rearrangement can occur after IgLλ rearrangement, (3) early formed B cells bear only single in-frame IgH rearrangements, (4) many IgLκ B cells carry IgLλ rearrangements that can be productive and occurring on both alleles in one cell, and (5) although VpreB and λ5 genes are present in swine, they are preferentially expressed in non-B cells. In summary, our findings reveal that swine use an alternative B cell developmental pathway as compared to mice and humans.
B 细胞淋巴生成的发育途径在小鼠和人类中研究得较为充分。然而,这两个物种的免疫球蛋白重链(IgH)重排在轻链(IgL)之前,而猪的 IgL 重排在 IgH 之前。我们在这里证明,这种重排顺序的颠倒有一些隐藏的后果:(1)我们证实,尽管 IgLκ 重排是初始的,但大多数 IgLλ B 细胞更早且在 IgH 重排之前产生,而大多数 IgLκ B 细胞更晚且在 IgH 重排之后产生,(2)第二个 IgLκ 重排可以在 IgLλ 重排之后发生,(3)早期形成的 B 细胞只携带单个框内 IgH 重排,(4)许多 IgLκ B 细胞携带 IgLλ 重排,这些重排可以在一个细胞的两个等位基因上发生并具有生产力,(5)尽管猪中存在 VpreB 和 λ5 基因,但它们优先在非 B 细胞中表达。总之,我们的研究结果表明,与小鼠和人类相比,猪使用了一种替代的 B 细胞发育途径。