Kitamura D, Roes J, Kühn R, Rajewsky K
Institute for Genetics, University of Cologne, Germany.
Nature. 1991 Apr 4;350(6317):423-6. doi: 10.1038/350423a0.
Of the various classes of antibodies that B lymphocytes can produce, class M (IgM) is the first to be expressed on the membrane of the developing cells. Pre-B cells, the precursors of B-lymphocytes, produce the heavy chain of IgM (mu chain), but not light chains. Recent data suggest that pre-B cells express mu chains on the membrane together with the 'surrogate' light chains lambda 5 and V pre B (refs 2-7). This complex could control pre-B-cell differentiation, in particular the rearrangement of the light-chain genes. We have now assessed the importance of the membrane form of the mu chain in B-cell development by generating mice lacking this chain. We disrupted one of the membrane exons of the gene encoding the mu-chain constant region by gene targeting in mouse embryonic stem cells. From these cells we derived mice heterozygous or homozygous for the mutation. B-cell development in the heterozygous mice seemed to be normal, but in homozygous animals B cells were absent, their development already being arrested at the stage of pre-B-cell maturation.
在B淋巴细胞能够产生的各类抗体中，M类（IgM）是最早在发育中细胞的膜上表达的。前B细胞是B淋巴细胞的前体，可产生IgM的重链（μ链），但不产生轻链。最近的数据表明，前B细胞在膜上表达μ链，同时还表达“替代”轻链λ5和VpreB（参考文献2 - 7）。这种复合物可能控制前B细胞的分化，特别是轻链基因的重排。我们现在通过培育缺失该链的小鼠，评估了μ链膜形式在B细胞发育中的重要性。我们通过在小鼠胚胎干细胞中进行基因靶向，破坏了编码μ链恒定区的基因的一个膜外显子。从这些细胞中，我们培育出了该突变的杂合子或纯合子小鼠。杂合子小鼠中的B细胞发育似乎正常，但在纯合动物中，B细胞缺失，其发育在早B细胞成熟阶段就已停滞。
