Analysis of DHQ52 gene segment transcription and rearrangement during B-cell development in human fetal bone marrow.
Analysis of DHQ52 gene segment transcription and rearrangement during B-cell development in human fetal bone marrow.
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人胎儿骨髓 B 细胞发育过程中 DHQ52 基因片段转录和重排分析。
DOI:
10.1111/j.1749-6632.1995.tb55832.x
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发表时间:
1995
影响因子:
5.2
通讯作者:
SchroederJr,HW
中科院分区:
文献类型:
--
作者:
Bertrand3rd,FE;Billips,LG;SchroederJr,HW
Human B lymphopoiesis is a highly regulated process that occurs in the bone marrow where a pluripotent stem cell matures into an immunoglobulin-expressing B cell. The hallmark of this developmental pathway is somatic DNA rearrangement of the gene segments that encode the heavy and light chains of the antibody molecule. Rearrangement usually begins in the immunoglobulin heavy chain (IgH) locus with germline transcription of IgH gene segments. Next, one of 30 D, segments is joined to one of six JH elements. Subsequently, the DJ join undergoes rearrangement with one of about functional 50 VH segments, creating a complete heavy chain variable domain.'-4Although this process can potentially generate more than lo8 random combinations, the rearrangement process is regulated such that specific IgH gene segment combinations are preferred at different stages of human ontogeny. In particular, the DHQ52 gene segment is present in nearly 40% of VDJ and DJ IgH gene segment rearrangements in human fetal bone marrow. In contrast, DHQ52 is found in fewer than 1% of VDJ and DJ rearrangements in adult bone marrow and peripheral bl00d.~-~ Therefore, DJ rearrangement in fetal bone marrow may be regulated differently than in adult bone marrow. In order to precisely define the stages during which DHQ52 transcription and rearrangement may be regulated during human fetal B lymphopoiesis, fetal bone marrow cells were sorted into subpopulations representative of stem cell and progenitor, pro-B, pre-B I and 11, and B-cell populations on the basis of surface expression of the hematopoietic markers CD34, CD19, and IgM (FIG. 1). RT-PCR followed by Southern analysis was used to detect germline and rearranged DHQ52 DJ transcripts in each subpopulation.