Endogenous antibodies promote rapid myelin clearance and effective axon regeneration after nerve injury
Endogenous antibodies promote rapid myelin clearance and effective axon regeneration after nerve injury
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DOI：
10.1073/pnas.1001948107
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发表时间：
2010-06-29
影响因子：
11.1
通讯作者：
Barres, Ben A.
中科院分区：
文献类型：
--
作者：
Vargas, Mauricio E.;Watanabe, Junryo;Barres, Ben A.
退化的髓鞘质会抑制轴突再生，并在外周神经系统（PNS）损伤后被迅速清除，但中枢神经系统（CNS）损伤后不会被清除。为了更好地了解快速 PNS 髓磷脂清除的机制，我们测试了体液免疫系统的潜在作用。在这里，我们表明内源性抗体是快速、稳健的三七总皂苷髓磷脂清除和轴突再生所必需的。 B 细胞敲除 JHD 小鼠的巨噬细胞流入、髓磷脂清除和轴突再生显着延迟。在突变型 JHD 小鼠中，髓磷脂碎片的快速清除通过来自初始 WT 小鼠的抗体的被动转移或通过抗 PNS 髓磷脂抗体来恢复，但不是通过非神经抗体的递送。我们证明，退化的神经组织是预先存在的内源性抗体的目标，这些抗体通过促进巨噬细胞进入和吞噬活性来控制髓磷脂清除。这些结果证明了免疫球蛋白（Ig）在愈合过程中清除受损自身的作用，并表明中枢神经系统的免疫豁免状态可能导致中枢神经系统髓鞘清除和损伤后轴突再生失败。
Degenerating myelin inhibits axon regeneration and is rapidly cleared after peripheral (PNS) but not central nervous system (CNS) injury. To better understand mechanisms underlying rapid PNS myelin clearance, we tested the potential role of the humoral immune system. Here, we show that endogenous antibodies are required for rapid and robust PNS myelin clearance and axon regeneration. B-cell knockout JHD mice display a significant delay in macrophage influx, myelin clearance, and axon regeneration. Rapid clearance of myelin debris is restored in mutant JHD mice by passive transfer of antibodies from naive WT mice or by an anti-PNS myelin antibody, but not by delivery of nonneural antibodies. We demonstrate that degenerating nerve tissue is targeted by preexisting endogenous antibodies that control myelin clearance by promoting macrophage entrance and phagocytic activity. These results demonstrate a role for immunoglobulin (Ig) in clearing damaged self during healing and suggest that the immune-privileged status of the CNS may contribute to failure of CNS myelin clearance and axon regeneration after injury.