B4B, a novel growth-arrest gene, is expressed by a subset of progenitor/pre-B lymphocytes negative for cytoplasmic mu-chain.
B4B, a novel growth-arrest gene, is expressed by a subset of progenitor/pre-B lymphocytes negative for cytoplasmic mu-chain.
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DOI：
10.4049/jimmunol.157.1.72
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发表时间：
1996-07
影响因子：
4.4
通讯作者：
C. Ruegg;H. Y. Wu;F. Fagnoni;E. Engleman;R. Laus
中科院分区：
文献类型：
--
作者：
C. Ruegg;H. Y. Wu;F. Fagnoni;E. Engleman;R. Laus
我们对正常成人的 PBMC 进行密度分级，以富集包括早期免疫谱系前体的免疫母细胞部分。差异显示 PCR 实验鉴定出一种在该免疫母细胞部分中特异性表达的转录物。该 cDNA 被命名为 B4B，编码一种新的基因产物，包含四个假定的跨膜结构域。用抗 B4B Ig 检测到的 B4B+ 细胞在 PBMC 中的出现频率非常低 (0.01%)，并且在中等密度部分 (0.1-1.0%) 中显着富集。 B4B+ 细胞为 CD19+CD45+HLA-DR+，CD20、胞质 mu 链、CD3、CD16、CD56、CD34 和 CD68（单核细胞）阴性，与不表达胞质 mu 链的祖细胞/前 B 淋巴细胞亚群一致，因此可能缺乏生产性 Ig 重排。 B4B+ 子集的这种表型描述与我们的发现一致，即与 PBMC (0.01%) 相比，B4B+ 细胞在骨髓中的频率 (3-10%) 大大增加。 B4B 多肽序列仅与一种已知蛋白质 PMP-22/gas-3 表现出显着的同源性，PMP-22/gas-3 是一种诱导细胞生长停滞的雪旺细胞特异性蛋白质。 B4B 的瞬时表达特异性抑制细胞增殖超过 50%。基于其抗增殖作用和仅限于未成熟 B 细胞亚群的表达模式，B4B 基因产物可能参与 Ig 基因座的生产性 VDJC 重排之前 B 细胞的消除，或者参与转化的祖 B 细胞的生长停滞。
We subjected PBMC of normal adults to density fractionation to enrich for an immunoblast fraction that would include early immune lineage precursors. Differential display PCR experiments identified one transcript that is expressed specifically in this immunoblast fraction. This cDNA, designated B4B, encodes a novel gene product containing four putative transmembrane-spanning domains. B4B+ cells, detected with anti-B4B Ig, were found at very low frequency in PBMC (0.01%) and were enriched significantly in intermediate density fractions (0.1-1.0%). B4B+ cells were shown to be CD19+CD45+HLA-DR+ and negative for CD20, cytoplasmic mu-chain, CD3, CD16, CD56, CD34, and CD68 (monocyte), consistent with a progenitor/pre-B lymphocyte subset that does not express cytoplasmic mu-chain and thus may lack productive Ig rearrangement. This phenotypic description of the B4B+ subset agrees with our finding that the frequency of B4B+ cells was greatly increased in bone marrow (3-10%) as compared with PBMC (0.01%). The B4B polypeptide sequence exhibits significant homology to only one known protein, PMP-22/gas-3, a Schwann cell-specific protein that induces cell growth arrest. Transient expression of B4B specifically inhibited cellular proliferation by more than 50%. Based on its antiproliferative effect and pattern of expression restricted to a subpopulation of immature B cells, the B4B gene product may be involved in the elimination of B cells before productive VDJC rearrangement of Ig loci or, alternatively, in the growth arrest of transformed progenitor B cells.