B cells regulate antibody responses through the medullary remodeling of inflamed lymph nodes
B cells regulate antibody responses through the medullary remodeling of inflamed lymph nodes
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DOI：
10.1093/intimm/dxr089
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发表时间：
2012-01-01
影响因子：
4.4
通讯作者：
Matsushima, Kouji
中科院分区：
文献类型：
--
作者：
Abe, Jun;Ueha, Satoshi;Matsushima, Kouji
淋巴结（LN）结构在免疫反应过程中被重塑，这一过程被认为在免疫功能的调节中发挥重要作用。迄今为止，尽管髓质区域被认为是产生抗体的浆细胞的利基，但它的重塑却很少受到关注。在这里，我们发现 B 细胞在炎症过程中介导抗原排出 LN 的髓质重塑。这一过程的发生动力学类似于浆细胞数量的变化，并伴随着基质重新网络化，表现为 B 细胞和浆细胞的分离。髓质重塑依赖于通过淋巴毒素-β受体的信号传导和 B 细胞的存在，但其发生独立于 T 依赖性体液反应或其他免疫细胞亚群（包括 T 细胞、单核细胞和中性粒细胞）。此外，在 B 细胞缺陷小鼠中重建非同源多克隆 B 细胞不仅恢复了髓质重塑，还恢复了单独转移的同源 B 细胞的抗体反应，表明非同源 B 细胞通过髓质重塑促进了抗体反应。我们提出非同源 B 细胞通过髓质重塑介导 LN 浆细胞生态位的扩张，从而调节 LN 浆细胞库的大小。
Lymph node (LN) structure is remodeled during immune responses, a process which is considered to play an important role in the regulation of immune function. To date, little attention has been paid to the remodeling of the medullary region, despite its proposed role as a niche for antibody-producing plasma cells. Here, we show that B cells mediate medullary remodeling of antigen-draining LNs during inflammation. This process occurs with kinetics similar to changes in plasma cell number and is accompanied by stromal renetworking which manifests as the segregation of B cells and plasma cells. Medullary remodeling depends on signaling via the lymphotoxin-beta receptor and the presence of B cells but occurs independently of T-dependent humoral responses or other immune cell subsets including T cells, monocytes and neutrophils. Moreover, reconstitution of non-cognate polyclonal B cells in B cell-deficient mice restores not only the medullary remodeling but also the antibody response by separately transferred cognate B cells, suggesting that non-cognate B cells contribute to antibody responses through medullary remodeling. We propose that non-cognate B cells mediate the expansion of the plasma cell niche in LN through medullary remodeling, thereby regulating the size of the LN plasma cell pool.