Tiller Thomas, Tsuiji Makoto, Yurasov Sergey, Velinzon Klara, Nussenzweig Michel C, Wardemann Hedda
Max-Planck-Institute for Infection Biology, D-10117 Berlin, Germany.
Immunity. 2007 Feb;26(2):205-13. doi: 10.1016/j.immuni.2007.01.009.
More than half of the nascent B cells in humans initially express autoreactive antibodies. However, most of these autoantibodies are removed from the repertoire at two checkpoints before maturation into naive B cells. A third checkpoint excludes remaining autoantibodies from the antigen-experienced IgM(+) memory B cell pool. Nevertheless, low-affinity self-reactive antibodies are frequently found in the serum of normal humans. To determine the source of these antibodies, we cloned and expressed antibodies from circulating human IgG(+) memory B cells. Surprisingly, we found that self-reactive antibodies including anti-nuclear antibodies were frequently expressed by IgG(+) memory B cells in healthy donors. Most of these antibodies were created de novo by somatic hypermutation during the transition between mature naive and IgG(+) memory B cells. We conclude that deregulation of self-reactive IgG(+) memory B cells may be associated with autoimmunity.
人类中超过一半的新生B细胞最初会表达自身反应性抗体。然而，在这些自身抗体成熟为未成熟B细胞之前，其中大部分会在两个检查点从抗体库中被清除。第三个检查点则将剩余的自身抗体排除在经历过抗原刺激的IgM(+)记忆B细胞库之外。尽管如此，正常人类血清中仍经常能发现低亲和力的自身反应性抗体。为了确定这些抗体的来源，我们克隆并表达了循环中的人类IgG(+)记忆B细胞中的抗体。令人惊讶的是，我们发现包括抗核抗体在内的自身反应性抗体在健康供体的IgG(+)记忆B细胞中经常表达。这些抗体中的大多数是在成熟未成熟B细胞向IgG(+)记忆B细胞转变过程中通过体细胞高频突变重新产生的。我们得出结论，自身反应性IgG(+)记忆B细胞的失调可能与自身免疫有关。
