Resolution of three nonproliferative immature splenic B cell subsets reveals multiple selection points during peripheral B cell maturation
Resolution of three nonproliferative immature splenic B cell subsets reveals multiple selection points during peripheral B cell maturation
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DOI：
10.4049/jimmunol.167.12.6834
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发表时间：
2001-12-15
影响因子：
4.4
通讯作者：
Hardy, RR
中科院分区：
文献类型：
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作者：
Allman, D;Lindsley, RC;Hardy, RR
尽管未成熟/过渡性外周 B 细胞在完全成熟之前可能仍然容易受到选择压力的影响，但这些选择事件的性质和时间仍不清楚。我们发现表面 IgM (sIgM)、CD23 和 AA4 的相关表达定义了未成熟/过渡性外周 B 细胞的三个非增殖亚群。我们将这些群体指定为过渡型 (T) 1（AA4(+)CD23(-)sIgM（高））、T2（AA4（+）CD23（+）sIgM（高））和 T3（AA4（+）CD23（+）sIgM（高））。根据体外 sIgM 交联后无法增殖以及通过 5-溴-2'-脱氧尿苷标记评估的体内快速周转率来判断，所有三个亚群内的细胞功能不成熟。这些标记研究还揭示了 T1-T2 和 T2-T3 转变时可测量的细胞损失，表明外周未成熟 B 细胞库中存在多个选择点。此外，我们发现 Btk 缺陷 (xid) 小鼠在未成熟 B 细胞库中的 T2-T3 转变时表现出不完全发育障碍。这与 lyn(-/-) 小鼠形成鲜明对比，lyn(-/-) 小鼠的未成熟外周 B 细胞亚群数量减少，但比例正常，成熟 B 细胞数量严重减少。总之，这些数据为未成熟外周 B 细胞中的多个选择点提供了证据，表明 B 细胞库是由未成熟/过渡外周 B 细胞池内发生的多个独特选择事件形成的。
Although immature/transitional peripheral B cells may remain susceptible to selection pressures before full maturation, the nature and timing of these selection events remain unclear. We show that correlated expression of surface (s) IgM (sIgM), CD23, and AA4 defines three nonproliferative subpopulations of immature/transitional peripheral B cells. We designate these populations transitional (T) 1 (AA4(+)CD23(-)sIgM(high)), T2 (AA4(+)CD23(+)sIgM(high)), and T3 (AA4(+)CD23(+)sIgM(high)). Cells within all three subsets are functionally immature as judged by their failure to proliferate following sIgM cross-linking in vitro, and their rapid rate of turnover in vivo as assessed by 5-bromo-2'-deoxyuridine labeling. These labeling studies also reveal measurable cell loss at both the T1-T2 and T2-T3 transitions, suggesting the existence of multiple selection points within the peripheral immature B cell pool. Furthermore, we find that Btk-deficient (xid) mice exhibit an incomplete developmental block at the T2-T3 transition within the immature B cell pool. This contrasts markedly with lyn(-/-) mice, which exhibit depressed numbers but normal ratios of each immature peripheral B cell subset and severely reduced numbers of mature B cells. Together, these data provide evidence for multiple selection points among immature peripheral B cells, suggesting that the B cell repertoire is shaped by multiple unique selection events that occur within the immature/transitional peripheral B cell pool.