Immature B cells preferentially switch to IgE with increased direct Sμ to Sε recombination.

Immature B cells preferentially switch to IgE with increased direct Sμ to Sε recombination.
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DOI:
10.1084/jem.20111155
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发表时间:
2011-12-19
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Alt FW
Alt FW
中科院分区:
其他
文献类型:
--
作者:
Wesemann DR;Magee JM;Boboila C;Calado DP;Gallagher MP;Portuguese AJ;Manis JP;Zhou X;Recher M;Rajewsky K;Notarangelo LD;Alt FW

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有待补充。免疫球蛋白重链(IgH)类开关重组将最初表达的Cμ恒定区(CH)外显子替换为下游CH外显子。抗CD_(40)+IL-4刺激B细胞可诱导CSR由C-μ向C-γ-1和C-ε转化,后者参与了特应性疾病的发病过程。虽然CεCSR可直接由Cμ发生,但大多数成熟的外周B细胞都间接地经历了CSR到Cε,即从Cμ到Cγ1,然后到Cε。影响C-γ-1和C-ε受体的生理机制还不完全清楚。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。部分基于一种新的流式细胞术分析,我们发现未成熟的B细胞通过增加从Cμ到Cε的直接CSR而优先转换为IgE而不是IgG1型。我们的研究结果提示,某些免疫缺陷的IgE异常可能与B细胞成熟受损有关。
To be added. Immunoglobulin heavy chain (IgH) class-switch recombination (CSR) replaces initially expressed Cμ (IgM) constant regions (CH) exons with downstream CH 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.
分类哮喘的细胞因子。
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