Development of V(H)81X transgene-bearing B cells in fetus and adult: Sites for expansion and deletion in conventional and CD5/B1 cells
Development of V(H)81X transgene-bearing B cells in fetus and adult: Sites for expansion and deletion in conventional and CD5/B1 cells
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DOI：
10.1093/intimm/9.4.493
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发表时间：
1997-04-01
影响因子：
4.4
通讯作者：
Kearney, JF
中科院分区：
文献类型：
--
作者：
Martin, F;Chen, XJ;Kearney, JF
最接近D端的功能性V-H基因V（H）81 X优先在小鼠胎儿B细胞库中表达;然而，它在成人的少数B细胞中表达。为了确定V（H）81 X基因表达何时影响B细胞分化中特定阶段的大小和表型，已经开发了表达生殖系胎肝衍生的V（H）81 X-mu重排的转基因小鼠。对B淋巴细胞生成的比较分析揭示了胎肝和成人骨髓之间的相似性和差异，其精确定位了小鼠中表达V（H）81 X的B细胞祖细胞扩增或耗尽隔室大小的发育阶段。这些包括c-kitR（+）的类似减少和在B220（+）CD 43（+）区室内主要CD 43（低）/HSA（高）表型的建立，这取决于转基因与λ 5的缔合。相反，CD 43（-）前B和未成熟的a细胞区室在胎儿中扩增，但在成人中不扩增。此外，还有其他因素不利于表达V（H）81 X的B1和B2细胞的存活。因此，未能在成人中检测到携带V（H）81 X的a细胞是在库扩增期间的所有阶段发生的多步选择过程的结果。
The most D-proximal functional V-H gene, V(H)81X, is preferentially expressed in the mouse fetal B cell repertoire; however, it is expressed in few B cells in the adult. To determine when V(H)81X gene expression affects size and phenotype of particular stages in B cell differentiation, transgenic mice have been developed expressing a germline fetal liver-derived V(H)81X-mu rearrangement. Comparative analysis of B lymphopoiesis reveals similarities and differences between fetal liver and adult bone marrow which pinpoint developmental stages in mice during which V(H)81X-expressing B cell progenitors expand or deplete compartment sizes. These include a similar reduction in c-kitR(+) and establishment of a predominant CD43(low)/HSA(high) phenotype within the B220(+)CD43(+) compartment which is dependent on the association of the transgene with lambda 5. In contrast, the CD43(-) pre-B and immature a cell compartments are expanded in the fetus but not in the adult. In addition, there are other factors that later disfavor the survival of V(H)81X-expressing B1 and B2 cells. Thus the failure to detect V(H)81X-bearing a cells in the adult is the result of a multistep selection process occurring at all stages during a repertoire expansion.