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一个功能性B细胞受体转基因可使B细胞前体在不依赖白细胞介素-7的情况下高效成熟。

A functional B cell receptor transgene allows efficient IL-7-independent maturation of B cell precursors.

作者信息

Melamed D, Kench J A, Grabstein K, Rolink A, Nemazee D

机构信息

Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.

出版信息

J Immunol. 1997 Aug 1;159(3):1233-9.

PMID:9233618
Abstract

IL-7 supports the proliferation of B cell precursors, but inhibits their maturation to mature surface IgM+ (sIgM+) B cells. This inhibition is thought to occur by direct or indirect down-regulation of recombinase genes, preventing the B cells from undergoing Ig light chain rearrangements. To directly analyze the IL-7 inhibitory effects, we studied B cell development and maturation in B cells bearing a transgenic (Tg) B cell receptor (BCR). We show here that proliferation of Tg B cell precursors is IL-7 dependent both in vivo and in vitro and is comparable to that of non-Tg B cell precursors. Tg B cell precursors grown on stroma and IL-7 expressed sIgM on >90% of the cells, and a large proportion of these cells coexpressed additional maturation markers such as IgD, CD23, CD21, and L-selectin, indicating that IL-7 does not inhibit maturation of Tg B cell precursors. The presence of the Tg inhibited V(D)J recombination in the cultured cells, as very low levels of recombination activating genes 2 (RAG-2) expression and endogenous V-Jkappa DNA rearrangements were found. Expression levels of RAG mRNAs were not significantly changed after removal of IL-7 from the in vitro Tg B cell cultures. In contrast, we found that IL-7 inhibited maturation of non-Tg B cell precursors and that removal of IL-7 resulted in a significant increase in RAG-2 expression and kappa rearrangements, thus allowing the B cells to express sIgM and to mature. These results suggest that IL-7-mediated inhibition of Ig gene rearrangement blocks maturation of B cell precursors and that the presence of Tg BCR efficiently circumvents this inhibition.

摘要

白细胞介素-7(IL-7)可支持B细胞前体的增殖,但会抑制它们成熟为表面免疫球蛋白M阳性(sIgM+)的成熟B细胞。这种抑制作用被认为是通过直接或间接下调重组酶基因来实现的,从而阻止B细胞进行免疫球蛋白轻链重排。为了直接分析IL-7的抑制作用,我们研究了携带转基因(Tg)B细胞受体(BCR)的B细胞的发育和成熟过程。我们在此表明,Tg B细胞前体的增殖在体内和体外均依赖IL-7,且与非Tg B细胞前体的增殖情况相当。在基质和IL-7上生长的Tg B细胞前体中,超过90%的细胞表达sIgM,并且这些细胞中的很大一部分还共表达了其他成熟标志物,如IgD、CD23、CD21和L-选择素,这表明IL-7不会抑制Tg B细胞前体的成熟。Tg的存在抑制了培养细胞中的V(D)J重组,因为发现重组激活基因2(RAG-2)的表达水平非常低,且存在内源性V-Jkappa DNA重排。从体外Tg B细胞培养物中去除IL-7后,RAG mRNA的表达水平没有显著变化。相反,我们发现IL-7抑制非Tg B细胞前体的成熟,去除IL-7会导致RAG-2表达和kappa重排显著增加,从而使B细胞能够表达sIgM并成熟。这些结果表明,IL-7介导的免疫球蛋白基因重排抑制会阻碍B细胞前体的成熟,而Tg BCR的存在有效地规避了这种抑制作用。

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