Identification of a Precursor to Phosphatidyl Choline-Specific B-1 Cells Suggesting That B-1 Cells Differentiate from Splenic Conventional B Cells In Vivo: Cyclosporin A Blocks Differentiation to B-11

Identification of a Precursor to Phosphatidyl Choline-Specific B-1 Cells Suggesting That B-1 Cells Differentiate from Splenic Conventional B Cells In Vivo: Cyclosporin A Blocks Differentiation to B-11
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磷脂酰胆碱特异性 B-1 细胞前体的鉴定表明 B-1 细胞在体内与脾脏常规 B 细胞分化:环孢素 A 阻止分化为 B-11

DOI:
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发表时间:
2000
影响因子:
4.4
通讯作者:
S. Clarke
S. Clarke
中科院分区:
医学2区
文献类型:
--
作者:
L. Arnold;S. McCray;C. Tatu;S. Clarke

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B-1细胞的起源是有争议的。最初的范式假设B-1和B-2细胞来自不同的谱系。最近有观点认为,B-1细胞来源于传统B细胞,是t非依赖性Ag活化的结果。为了了解B-1细胞的分化情况,我们利用抗磷脂酰胆碱(anti-PtC) B细胞的H链和L链基因(VH12和Vκ4)培育了Ig转基因(Tg)小鼠。在正常小鼠中,抗ptc B细胞分离为B-1。在VH12(6-1)和VH12/Vκ4(双)Tg小鼠中,分离是完整的,产生了大量ptc特异性B细胞。然而,如果B-1细胞分化被阻断,这些Tg小鼠中的抗ptc B细胞在表型上是B-2样的,这表明存在由ag驱动的B-2向B-1的分化途径。在这项研究中,我们发现双Tg小鼠具有抗ptc B细胞群,这些细胞具有B-2和B-1细胞的表型特征,并且具有向B-1 (B-1a和B-1b)分化的潜力。环孢素A阻断了这种分化,并在这些细胞中诱导了更类似b2的表型。这些发现表明这些细胞介于B-2和B-1之间,进一步证明了B-2到B-1的分化途径。
The origin of B-1 cells is controversial. The initial paradigm posited that B-1 and B-2 cells derive from separate lineages. More recently it has been argued that B-1 cells derive from conventional B cells as a result of T-independent Ag activation. To understand B-1 cell differentiation, we have generated Ig transgenic (Tg) mice using the H and L chain genes (VH12 and Vκ4) of anti-phosphatidyl choline (anti-PtC) B cells. In normal mice anti-PtC B cells segregate to B-1. Segregation is intact in VH12 (6-1) and VH12/Vκ4 (double) Tg mice that develop large numbers of PtC-specific B cells. However, if B-1 cell differentiation is blocked, anti-PtC B cells in these Tg mice are B-2-like in phenotype, suggesting the existence of an Ag-driven differentiative pathway from B-2 to B-1. In this study, we show that double Tg mice have a population of anti-PtC B cells that have the phenotypic characteristics of both B-2 and B-1 cells and that have the potential to differentiate to B-1 (B-1a and B-1b). Cyclosporin A blocks this differentiation and induces a more B-2-like phenotype in these cells. These findings indicate that these cells are intermediate between B-2 and B-1, further evidence of a B-2 to B-1 differentiative pathway.
成人 B 细胞库偏向于在胎儿前 B 细胞中频繁重排的两个重链可变区基因。
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