Selection of stereotyped VH81X-μH chains via pre-B cell receptor early in ontogeny and their conservation in adults by marginal zone B cells
Selection of stereotyped VH81X-μH chains via pre-B cell receptor early in ontogeny and their conservation in adults by marginal zone B cells
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DOI：
10.1093/intimm/dxh265
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发表时间：
2005-07-01
影响因子：
4.4
通讯作者：
Karasuyama, H
中科院分区：
文献类型：
--
作者：
Kawano, Y;Yoshikawa, S;Karasuyama, H
B细胞前受体（pre-B cell receptor, preBCR）在B细胞早期分化中起着至关重要的作用。研究表明，并非所有的mu H链都能与替代光链（SL）配对形成preBCR。在这里，我们建立了一个新的系统来区分鉴定小鼠骨髓和胎肝中的两种早期前b细胞群，一种产生sl -配对的mu H链，另一种产生sl -非配对的mu H链。前者占成人骨髓中所有早期前b细胞的80%，而在胎儿肝脏中仅占20%。通过对两种类型的胎儿肝脏前B细胞群的比较，揭示了由V(H)81X片段编码的sl -配对和-非配对mu H链的结构差异，V(H)81X片段在胎儿肝脏前B细胞中最常使用，而在成人生成的B细胞中很少表达。PreBCR在携带互补决定区3特征序列的V(H)81X-mu H链的阳性选择中发挥了重要作用，这些特征序列很少或不添加啃咬或N核苷酸，导致它们在新生儿脾B细胞中占主导地位。这些胎儿型V(H)81X-mu H链也在成人脾脏中检测到，但与成人型V(H)81X-mu H链相比，几乎只在边缘区（MZ） B细胞中检测到。这强烈表明，表达定型V(H)81X-mu H链的新生儿生成和选择的B细胞在成年MZ中维持，并可能具有先天样淋巴细胞的功能。
The pre-B cell receptor (preBCR) plays critical roles in early B cell differentiation. It has been shown that not all mu H chains are capable of pairing with surrogate light (SL) chains to form preBCR. Here, we established a novel system to differentially identify two types of early pre-B cell populations in bone marrow and fetal liver of mice, one producing SL-pairing mu H chains and the other producing SL-non-pairing mu H chains. The former population accounted for 80% of all the early pre-B cells in adult bone marrow, while it accounted for only 20% of those in fetal liver. Comparison of the two types of pre-B cell populations in fetal liver revealed the structural difference between SL-pairing and -non-pairing mu H chains encoded by the V(H)81X segment that was most frequently utilized in fetal liver pre-B cells but rarely expressed by B cells generated in adults. PreBCR played an important role in the positive selection of V(H)81X-mu H chains carrying the characteristic sequences of the complementarity-determining region 3 with little or no nibbling or N nucleotide addition, leading to their predominance in neonatal splenic B cells. These fetal-type V(H)81X-mu H chains were also detected in adult spleen, but almost exclusively in marginal zone (MZ) B cells in contrast to the adult-type V(H)81X-mu H chains. This strongly suggests that neonatally generated and selected B cells expressing the stereotyped V(H)81X-mu H chains are maintained in the adult MZ and could function as innate-like lymphocytes.