Generation of peripheral B cells occurs via two spatially and temporally distinct pathways

Generation of peripheral B cells occurs via two spatially and temporally distinct pathways
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DOI:
10.1182/blood-2006-04-018085
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发表时间:
2007-03-15
期刊:
影响因子:
20.3
通讯作者:
Allman, David
Allman, David
中科院分区:
医学1区
文献类型:
--
作者:
Lindsley, Robert Coleman;Thomas, Matthew;Allman, David

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我们已经确定了一个新形成的骨髓(BM) B细胞群体,它们与脾脏中晚期移行B细胞具有多种特征。脾脏晚期移行性B细胞和该未表征BM群体中的细胞均表达细胞表面表型AA4(+) CD23(+),但AA4(+) CD23(+) BM B细胞的发育动力学和更新率反映了BM和脾脏中最近最不成熟的B细胞,AA4(+) CD23(+) BM B细胞表达归巢受体CD62L,依赖于凋亡细胞因子受体BR3和tec家族激酶Btk,并在IL-4 + CD40刺激下增殖。最后,在BM和脾脏的AA4(+) CD23(+) B细胞中,lambda轻链阳性B细胞的频率下降,表明v -基因选择事件与两个区室中的CD23表达相关。这些观察结果表明,B细胞成熟的第一步发生在骨髓和外周,并表明新近形成的B细胞作为一个不成熟和半成熟B细胞的异质池退出骨髓。
We have identified a population of newly formed bone marrow (BM) B cells that shares multiple characteristics with late transitional B cells in the spleen. Both late splenic transitional B cells and cells within this uncharacterized BM population expressed the cell-surface phenotype AA4(+) CD23(+), yet the developmental kinetics and the renewal rate of AA4(+) CD23(+) BM B cells mirrored recently least mature B cells in the BM and spleen, AA4(+) CD23(+) BM B cells expressed the homing receptor CD62L, were dependent on the antlapoptotic cytokine receptor BR3 and the tec family kinase Btk, and proliferated in response to IL-4 plus CD40 stimulation. Finally, frequencies of lambda light chain-positive B cells declined among AA4(+) CD23(+) B cells in both the BM and spleen, suggesting that V-gene selection events correlate with CD23 expression in both compartments. These observations indicate that the first step in B-cell maturation occurs in both the BM and the periphery and suggest that recently formed B cells exit the BM as a heterogeneous pool of immature and semimature B cells.