Neuroimmune interactions are essential for the development of neuropathic pain, yet the contributions of distinct immune cell populations have not been fully unraveled. Here, we demonstrate the critical role of B cells in promoting mechanical hypersensitivity (allodynia) after peripheral nerve injury in male and female mice. Depletion of B cells with a single injection of anti-CD20 monoclonal antibody at the time of injury prevented the development of allodynia. B cell–deficient (muMT) mice were similarly spared from allodynia. Nerve injury was associated with increased immunoglobulin G (IgG) accumulation in ipsilateral lumbar dorsal root ganglia (DRGs) and dorsal spinal cords. IgG was colocalized with sensory neurons and macrophages in DRGs and microglia in spinal cords. IgG also accumulated in DRG samples from human donors with chronic pain, colocalizing with a marker for macrophages and satellite glia. RNA sequencing revealed a B cell population in naive mouse and human DRGs. A B cell transcriptional signature was enriched in DRGs from human donors with neuropathic pain. Passive transfer of IgG from injured mice induced allodynia in injured muMT recipient mice. The pronociceptive effects of IgG are likely mediated through immune complexes interacting with Fc gamma receptors (FcγRs) expressed by sensory neurons, microglia, and macrophages, given that both mechanical allodynia and hyperexcitability of dissociated DRG neurons were abolished in nerve-injured FcγR-deficient mice. Consistently, the pronociceptive effects of IgG passive transfer were lost in FcγR-deficient mice. These data reveal that a B cell–IgG–FcγR axis is required for the development of neuropathic pain in mice.

中文翻译：

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B 细胞通过 IgG-Fc γ 受体信号传导驱动小鼠神经性疼痛相关行为


神经免疫相互作用对于神经性疼痛的发展至关重要，但不同免疫细胞群的贡献尚未完全揭示。在这里，我们证明了 B 细胞在促进雄性和雌性小鼠周围神经损伤后机械超敏反应（异常性疼痛）中的关键作用。在受伤时单次注射抗 CD20 单克隆抗体会耗竭 B 细胞，从而防止了异常性疼痛的发展。B 细胞缺陷 （muMT） 小鼠同样不受异常性疼痛的影响。神经损伤与同侧腰背根神经节 （DRG） 和背脊髓免疫球蛋白 G （IgG） 积累增加有关。IgG 与 DRGs 中的感觉神经元和巨噬细胞以及脊髓中的小胶质细胞共定位。IgG 还在患有慢性疼痛的人类供体的 DRG 样本中积累，与巨噬细胞和卫星胶质细胞的标志物共定位。RNA 测序显示幼稚小鼠和人类 DRG 中存在 B 细胞群。A B 细胞转录特征在来自患有神经性疼痛的人类供体的 DRG 中富集。来自受伤小鼠的 IgG 被动转移诱导了受伤的 muMT 受体小鼠的异常性疼痛。IgG 的伤害感受作用可能是通过与感觉神经元、小胶质细胞和巨噬细胞表达的 Fc γ 受体 （FcγR） 相互作用的免疫复合物介导的，因为在神经损伤的 FcγR 缺陷小鼠中，解离的 DRG 神经元的机械异常性疼痛和过度兴奋都被消除。一致地，IgG 被动转移的伤害感受作用在 FcγR 缺陷小鼠中丢失。这些数据表明，B 细胞-IgG-FcγR 轴是小鼠神经性疼痛发展所必需的。