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小鼠B细胞库中从重排基因片段到免疫球蛋白合成的λ亚型保守分布。

Conserved distribution of lambda subtypes from rearranged gene segments to immunoglobulin synthesis in the mouse B cell repertoire.

作者信息

Boudinot P, Drapier A M, Cazenave P A, Sanchez P

机构信息

Départment d'Immunologie Institut Pasteur (UA CNRS 359), Paris, France.

出版信息

Eur J Immunol. 1994 Sep;24(9):2013-7. doi: 10.1002/eji.1830240912.

Abstract

The immunoglobulin lambda light chain system displays a limited diversity in inbred mice. Indeed, the lambda locus is organized in two recombination units: V lambda 2-V lambda x-J lambda 2-C lambda 2-psi J lambda 4-psi C lambda 4, which can produce either lambda 2(V2) or lambda 2(Vx) chains; and V lambda 1-J lambda 3-C lambda 3-J lambda 1-C lambda 1, which can produce either lambda 1 or lambda 3 chains. Each of these units is associated with an enhancer, E lambda 2-4 or E lambda 1-3, at the 3' side. The expression of each lambda chain is, therefore, controlled by distinct promoter and/or enhancer regions. To clarify the basis of these controls, we measured, by quantitative polymerase chain reaction, the proportions of each lambda subtype in BALB/c spleen mRNA and among genomic rearrangements. It appears that these distributions are similar to and consistent with the relative cellular frequencies in the spleen, as evaluated by flow cytometry. These results suggest that, in resting cells, the transcription rates are identical, regardless of the lambda subtype. After lipopolysaccharide (LPS) stimulation, the transcription rates per cell remain similar for all lambda subtypes despite different regulatory sequences. To detect eventual post-transcriptional regulations, we estimated the lambda light chain distribution in IgM secreted by LPS-stimulated B cells and in serum IgG. These distributions are still similar to those of lambda-expressing cells, lambda mRNA or genomic rearrangements. We conclude that the lambda subtype distribution is conserved from productive V-J rearranged genes to secreted lambda immunoglobulins, despite different regulatory sequences.

摘要

免疫球蛋白λ轻链系统在近交系小鼠中表现出有限的多样性。实际上,λ基因座由两个重组单元组成:Vλ2-Vλx-Jλ2-Cλ2-ψJλ4-ψCλ4,可产生λ2(V2)或λ2(Vx)链;以及Vλ1-Jλ3-Cλ3-Jλ1-Cλ1,可产生λ1或λ3链。这些单元中的每一个在3'端都与一个增强子Eλ2-4或Eλ1-3相关联。因此,每条λ链的表达都由不同的启动子和/或增强子区域控制。为了阐明这些调控的基础,我们通过定量聚合酶链反应测量了BALB/c脾mRNA中以及基因组重排中每种λ亚型的比例。通过流式细胞术评估,这些分布似乎与脾中的相对细胞频率相似且一致。这些结果表明,在静息细胞中,无论λ亚型如何,转录速率都是相同的。在脂多糖(LPS)刺激后,尽管调控序列不同,但所有λ亚型的每个细胞转录速率仍保持相似。为了检测最终的转录后调控,我们估计了LPS刺激的B细胞分泌的IgM和血清IgG中λ轻链的分布。这些分布仍然与表达λ的细胞、λmRNA或基因组重排的分布相似。我们得出结论,尽管调控序列不同,但从有生产性的V-J重排基因到分泌的λ免疫球蛋白,λ亚型分布是保守的。

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