Variable region gene analysis of B cell subsets derived from a 4-year-old child: somatically mutated memory B cells accumulate in the peripheral blood already at young age.
Variable region gene analysis of B cell subsets derived from a 4-year-old child: somatically mutated memory B cells accumulate in the peripheral blood already at young age.
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DOI：
10.1084/jem.180.4.1383
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发表时间：
1994-10-01
期刊：
影响因子：
--
通讯作者：
Rajewsky K
中科院分区：
文献类型：
--
作者：
Klein U;Küppers R;Rajewsky K
从一名4岁儿童的扁桃体生发中心和免疫球蛋白M+（IgM+）IgD+ B细胞以及外周血（PB）CD 5+和CD 5-（常规）B细胞中分离，并从扩增的cDNA中确定由VH 4基因家族成员编码的表达的IG重链可变区的核苷酸序列。而扁桃体IgM+IgD+细胞和大多数IgM表达的CD 5+和CD 5- PB B细胞显示没有或很少的体细胞突变，扁桃体生发中心（GC）B细胞和IgG表达的PB B细胞在其V区基因中携带高负荷的体细胞突变。这表明，体细胞突变的记忆B细胞已转换同种型积累在PB已经在年轻的年龄。频率似乎随着年龄的增长而增加。另一方面，扁桃体IgM+IgD+ B细胞和大多数表达IgM的PB B细胞的抗体库由种系编码的特异性和通过VH-DH-JH重组在互补决定区III中产生的变异性决定。一部分携带IgM的PB B细胞携带体细胞突变的V区基因，可能代表GC衍生的B细胞，其在GC反应的早期阶段离开GC而未经历同种型转换。发现10个VH 4生殖系基因表达。三个基因片段在序列集合中过度表达（50个克隆中的35个）：VH4.21（30%）、V71-4（20%）和3D 279 D（20%）。似乎大多数潜在功能性VH 4生殖系基因在外周B细胞中表达。这个VH基因家族的一些成员明显高于其他成员。
Tonsillar germinal center and immunoglobulin M+ (IgM+)IgD+ B cells as well as peripheral blood (PB) CD5+ and CD5- (conventional) B cells from a 4-yr-old child were isolated and nucleotide sequences of expressed Ig heavy chain variable regions encoded by VH4 gene family members were determined from amplified cDNA. Whereas both tonsillar IgM+IgD+ cells and the majority of IgM-expressing CD5+ and CD5- PB B cells showed no or little somatic mutation, tonsillar germinal center (GC) B cells and IgG-expressing PB B cells carried a high load of somatic mutations in their V region genes. This suggests that somatically mutated memory B cells which have switched isotype accumulate in the PB already at young age. Their frequency seems to increase with age. On the other hand, the antibody repertoire of tonsillar IgM+IgD+ B cells and the majority of IgM-expressing PB B cells is determined by germline-encoded specificities and by generation of variability in the complementary determining region III through VH-DH-JH recombination. A fraction of IgM-bearing PB B cells carries somatically mutated V region genes and probably represents GC-derived B cells which have left the GC at an early stage of the GC reaction without undergoing isotype switching. 10 VH4 germline genes were found to be expressed. Three gene segments were overrepresented in the sequence collection (35 of 50 clones): VH4.21 (30%), V71-4 (20%), and 3D279D (20%). It appears that most potentially functional VH4 germline genes are expressed in peripheral B cells. Some members of this VH gene family are clearly overrepresented over others.