Department of Biomedicine, University of Basel, Basel, Switzerland.
Eur J Immunol. 2012 Jan;42(1):206-16. doi: 10.1002/eji.201141957. Epub 2011 Dec 5.
The interaction between BAFF and BAFF-R is crucial for the development of mature B cells. Here, we report that the expression of BAFF-R is first detectable on a fraction of mouse CD19(+) CD93(+) IgM(+) CD23(-) and human CD19(+) CD10(+) IgM(+) BM B cells. This BAFF-R(+) BM B-cell population shows higher levels of surface IgM expression and decreased RAG-2 transcripts than BAFF-R(-) immature B cells. When cultured, mouse BAFF-R(-), but not BAFF-R(+) immature B cells spontaneously undergo B-cell receptor editing. However, BAFF-R(+) immature B cells cultured in the presence of an anti-κ light chain antibody are induced to undergo receptor editing. This receptor editing correlates with down-modulation of surface BAFF-R expression and the up-regulation of RAG-2 at the RNA level. B-cell receptor (BCR) cross-linking on splenic T1 B cells results in down-modulation of the BAFF-R, and receptor editing and RAG-2 up-regulation in a minor fraction of B cells. BCR cross-linking on splenic T2/3 B cells results in partly down and partly up-modulation of BAFF-R expression and no evidence for receptor editing. Overall, our data indicate that BAFF-R expression is tightly regulated during B-cell development in mouse and human and its expression is correlated with positive selection.
BAFF 和 BAFF-R 之间的相互作用对成熟 B 细胞的发育至关重要。在这里,我们报告说,BAFF-R 的表达首先可以在小鼠 CD19(+) CD93(+) IgM(+) CD23(-)和人类 CD19(+) CD10(+) IgM(+) BM B 细胞的一部分上检测到。与 BAFF-R(-)未成熟 B 细胞相比,这种 BAFF-R(+) BM B 细胞群体表现出更高水平的表面 IgM 表达和减少的 RAG-2 转录本。当培养时,小鼠 BAFF-R(-),而不是 BAFF-R(+)未成熟 B 细胞自发地经历 B 细胞受体编辑。然而,在存在抗 κ 轻链抗体的情况下培养 BAFF-R(+)未成熟 B 细胞会诱导其发生受体编辑。这种受体编辑与表面 BAFF-R 表达的下调和 RNA 水平上 RAG-2 的上调相关。在脾脏 T1 B 细胞上交联 B 细胞受体 (BCR) 会导致 BAFF-R 的下调,以及受体编辑和 RAG-2 的上调,这在一小部分 B 细胞中发生。在脾脏 T2/3 B 细胞上交联 BCR 会导致 BAFF-R 表达部分下调和部分上调,并且没有证据表明受体编辑。总体而言,我们的数据表明,BAFF-R 的表达在小鼠和人类的 B 细胞发育过程中受到严格调控,其表达与阳性选择相关。