Censoring of autoreactive B cell development by the pre-B cell receptor
Censoring of autoreactive B cell development by the pre-B cell receptor
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DOI：
10.1126/science.1157533
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发表时间：
2008-08-01
期刊：
影响因子：
56.9
通讯作者：
Martensson, Inga-Lill
中科院分区：
文献类型：
--
作者：
Keenan, Rebecca A.;De Riva, Alessandra;Martensson, Inga-Lill
当B细胞在发育过程中重组其免疫球蛋白(Ig)重链和轻链基因时，抗体多样性随机发生。这一过程不可避免地产生了对自身结构的反应性，几种机制阻止了自身反应性B细胞的发展。在此，我们报告了由免疫球蛋白重链和替代轻链组成的前B细胞受体在表达免疫球蛋白重链的细胞产生自身抗体的阴性选择中的作用。替代轻链缺陷(SLC-/-)小鼠血清中抗核抗体(ANA)水平升高，并显示出表达原型自身抗体重链的前B细胞逃避阴性选择的证据，导致成熟自身抗体在外围分泌CD21(-)CD23(-)B细胞。因此，前B细胞受体似乎审查某些自身抗体分泌细胞的发育，并可能代表多因素自身免疫性疾病的一个重要因素。
Antibody diversity occurs randomly as B cells recombine their immunoglobulin ( Ig) heavy- and light- chain genes during development. This process inevitably generates reactivity against self structures, and several mechanisms prevent the development of autoreactive B cells. We report here a role for the pre- B cell receptor, composed of Ig heavy and surrogate light chains, in the negative selection of cells expressing Ig heavy chains with the potential to generate autoantibodies. Surrogate light- chain- deficient (SLC-/-) mice harbored elevated levels of antinuclear antibodies (ANAs) in their serum and showed evidence of escape of pre- B cells expressing prototypic autoantibody heavy chains from negative selection, leading to mature autoantibody secreting CD21(-)CD23(-) B cells in the periphery. Thus, the pre- B cell receptor appears to censor the development of certain autoantibody- secreting cells and may represent an important factor in multifactorial autoimmune diseases.