Matsumoto M, Lo S F, Carruthers C J, Min J, Mariathasan S, Huang G, Plas D R, Martin S M, Geha R S, Nahm M H, Chaplin D D
Center for Immunology and Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Nature. 1996 Aug 1;382(6590):462-6. doi: 10.1038/382462a0.
Affinity maturation by somatic hypermutation is thought to occur within germinal centres. Mice deficient in lymphotoxin-alpha (LT alpha-/- mice) have no lymph nodes or Peyer's patches, and fail to form germinal centres in the spleen. We tested whether germinal centres are essential for maturation of antibody responses to T-cell-dependent antigens. LT alpha-/- mice immunized with low doses of (4-hydroxy-3-nitrophenyl)acetyl-ovalbumin (NP-OVA) showed dramatically impaired production of high-affinity anti-NP IgG1. However, LT alpha-/- mice immunized with high doses of NP-OVA, even though they failed to produce germinal centres, manifested a high-affinity anti-NP IgG1 response similar to wild-type mice. Furthermore, when LT alpha-/- mice were multiply immunized with high doses of NP-OVA, the predominantly expressed anti-NP VH gene segment VH186.2 showed somatic mutations typical of affinity maturation. Thus, B-cell memory and affinity maturation are not absolutely dependent on the presence of germinal centres.
体细胞高频突变导致的亲和力成熟被认为发生在生发中心内。缺乏淋巴毒素α的小鼠（LTα-/-小鼠）没有淋巴结或派尔集合淋巴结，并且脾脏中无法形成生发中心。我们测试了生发中心对于T细胞依赖性抗原抗体反应成熟是否必不可少。用低剂量（4-羟基-3-硝基苯基）乙酰卵清蛋白（NP-OVA）免疫的LTα-/-小鼠显示出高亲和力抗NP IgG1的产生显著受损。然而，用高剂量NP-OVA免疫的LTα-/-小鼠，尽管它们未能产生生发中心，但表现出与野生型小鼠相似的高亲和力抗NP IgG1反应。此外，当用高剂量NP-OVA多次免疫LTα-/-小鼠时，主要表达的抗NP VH基因片段VH186.2显示出亲和力成熟典型的体细胞突变。因此，B细胞记忆和亲和力成熟并不绝对依赖于生发中心的存在。
