Antigen receptor editing in anti-DNA transitional B cells deficient for surface IgM
Antigen receptor editing in anti-DNA transitional B cells deficient for surface IgM
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DOI：
10.4049/jimmunol.180.9.6094
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发表时间：
2008-05-01
影响因子：
4.4
通讯作者：
Bosma, Melvin J.
中科院分区：
文献类型：
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作者：
Kiefer, Kerstin;Nakajima, Pamela B.;Bosma, Melvin J.
为了应对自身 Ag 的遭遇，自身反应性 B 细胞可能会发生次级 L 链基因重排（受体编辑）并改变其 Ag 受体的特异性。了解发育中的 B 细胞在哪个分化阶段进行受体编辑对于了解自身反应性 B 细胞如何受到调节非常重要。在这项研究中，在具有编码抗自身（DNA）抗体的 Ig 转基因的小鼠中，我们报告了 dsDNA 断裂，这表明不仅在具有前 B/B 细胞表型的骨髓细胞中而且在表面 IgM 很少或没有的未成熟/移行脾 B 细胞中（sIgM（-/低））正在进行二级 L 链重排。 L链编辑的转基因B细胞在脾脏中可检测到，但在骨髓中却检测不到，并且仍然被发现产生对DNA（和凋亡细胞）具有特异性的抗体，尽管其对DNA的亲和力比未编辑的转基因抗体低。我们得出的结论是，抗 DNA 转基因 B 细胞中的 L 链编辑不仅在骨髓中进行，而且也在脾脏中进行。事实上，将 sIgM（-/低）抗 DNA 脾 B 细胞转移到 SCID 小鼠中，导致移植受体的血清中出现 L 链编辑器 (V lambda x)。最后，我们还报告了野生型小鼠 sIgM（低）过渡性脾 B 细胞中正在进行的 L 链编辑的证据。
In response to encounter with self-Ag, autoreactive B cells may undergo secondary L chain gene rearrangement (receptor editing) and change the specificity of their Ag receptor. Knowing at what differentiative stage(s) developing B cells undergo receptor editing is important for understanding how self-reactive B cells are regulated. In this study, in mice with Ig transgenes coding for anti-self (DNA) Ab, we report dsDNA breaks indicative of ongoing secondary L chain rearrangement not only in bone marrow cells with a pre-B/B cell phenotype but also in immature/transitional splenic B cells with little or no surface IgM (sIgM(-/low)). L chain-edited transgenic B cells were detectable in spleen but not bone marrow and were still found to produce Ab specific for DNA (and apoptotic cells), albeit with lower affinity for DNA than the unedited transgenic Ab. We conclude that L chain editing in anti-DNA-transgenic B cells is not only ongoing in bone marrow but also in spleen. Indeed, transfer of sIgM(-/low) anti-DNA splenic B cells into SCID mice resulted in the appearance of a L chain editor (V lambda x) in the serum of engrafted recipients. Finally, we also report evidence for ongoing L chain editing in sIgM(low) transitional splenic B cells of wild-type mice.