Program in Cellular and Molecular Medicine and Immune Disease Institute, Children's Hospital Boston, MA 02115, USA.
J Exp Med. 2011 Dec 19;208(13):2733-46. doi: 10.1084/jem.20111155. Epub 2011 Dec 5.
Immunoglobulin heavy chain (IgH) class-switch recombination (CSR) replaces initially expressed Cμ (IgM) constant regions (C(H)) exons with downstream C(H) exons. Stimulation of B cells with anti-CD40 plus interleukin-4 induces CSR from Cμ to Cγ1 (IgG1) and Cε (IgE), the latter of which contributes to the pathogenesis of atopic diseases. Although Cε CSR can occur directly from Cμ, most mature peripheral B cells undergo CSR to Cε indirectly, namely from Cμ to Cγ1, and subsequently to Cε. Physiological mechanisms that influence CSR to Cγ1 versus Cε are incompletely understood. In this study, we report a role for B cell developmental maturity in IgE CSR. Based in part on a novel flow cytometric IgE CSR assay, we show that immature B cells preferentially switch to IgE versus IgG1 through a mechanism involving increased direct CSR from Cμ to Cε. Our findings suggest that IgE dysregulation in certain immunodeficiencies may be related to impaired B cell maturation.
免疫球蛋白重链（IgH）类别转换重组（CSR）用下游的 C（H）外显子替换最初表达的 Cμ（IgM）恒定区（C（H））外显子。用抗 CD40 加白细胞介素 4 刺激 B 细胞可诱导 Cμ 向 Cγ1（IgG1）和 Cε（IgE）的 CSR，后者有助于特应性疾病的发病机制。尽管 Cε CSR 可以直接从 Cμ 发生，但大多数成熟的外周 B 细胞间接地从 Cμ 到 Cγ1，然后到 Cε 进行 CSR。影响 CSR 到 Cγ1 与 Cε 的生理机制尚未完全了解。在这项研究中，我们报告了 B 细胞发育成熟在 IgE CSR 中的作用。部分基于新型流式细胞术 IgE CSR 测定法，我们表明不成熟的 B 细胞通过涉及从 Cμ 到 Cε 的直接 CSR 增加的机制优先转换为 IgE 而不是 IgG1。我们的发现表明，某些免疫缺陷中 IgE 的失调可能与 B 细胞成熟受损有关。
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