van Loo Pieter Fokko, Dingjan Gemma M, Maas Alex, Hendriks Rudi W
Department of Immunology, Erasmus Medical Center Rotterdam, P.O. Box 2040, NL-3000 CA Rotterdam, The Netherlands.
Immunity. 2007 Sep;27(3):468-80. doi: 10.1016/j.immuni.2007.07.018.
The pre-B cell receptor (pre-BCR), composed of immunoglobulin mu heavy chain and the surrogate light chain (SLC) proteins lambda5 and Vpreb, signals for proliferation and maturation of developing pre-B cells. It has been assumed that pre-B cells stop cycling by the pre-BCR-mediated downregulation of SLC transcription. We generated transgenic mice expressing SLC throughout B cell development and, remarkably, found that enforced SLC expression had no effect on pre-B cell proliferation or differentiation. However, in the presence of conventional immunoglobulin light chains, SLC components had the capacity to induce constitutive BCR internalization, secondary immunoglobulin light-chain rearrangement, and a severe developmental arrest of immature B cells, dependent on the adaptor protein Slp65. Residual B cells in the spleen showed increased expression of surface CD5, which is a negative regulator of BCR signaling, and differentiated spontaneously into IgM+ plasma cells. Thus, the silencing of SLC genes is not essential for the limitation of pre-B cell proliferation, but is required for the prevention of constitutive activation of B cells.
前B细胞受体（pre-BCR）由免疫球蛋白μ重链和替代轻链（SLC）蛋白λ5及Vpreb组成，它为发育中的前B细胞的增殖和成熟发出信号。一直以来人们认为前B细胞通过前BCR介导的SLC转录下调而停止循环。我们构建了在整个B细胞发育过程中表达SLC的转基因小鼠，并且，值得注意的是，发现强制表达SLC对前B细胞的增殖或分化没有影响。然而，在存在常规免疫球蛋白轻链的情况下，SLC组分有能力诱导组成型BCR内化、二次免疫球蛋白轻链重排以及未成熟B细胞的严重发育停滞，这依赖于衔接蛋白Slp65。脾脏中的残余B细胞显示表面CD5表达增加，CD5是BCR信号传导的负调节因子，并且会自发分化为IgM+浆细胞。因此，SLC基因的沉默对于限制前B细胞增殖并非必不可少，但对于防止B细胞的组成型激活是必需的。
