Key Points BAFF increases in myeloid subsets in a cell- and tissue-specific manner. Neutrophil and DC BAFF are required for optimal T cell–independent 2 humoral responses. BAFF produced by DCs is required for protective immunity to West Nile virus. B cell activating factor (BAFF) is essential for B cells to develop and respond to Ags. Dysregulation of BAFF contributes to the development of some autoimmune diseases and malignancies. Little is known about when, where, and how BAFF is produced in vivo and about which BAFF-producing cells contribute to B cell responses. To better understand BAFF functions, we created BAFF reporter (BAFF-RFP) mice and Baff floxed (Bafffl/fl) mice. Splenic and bone marrow neutrophils (Nphs) from BAFF-RFP mice expressed the highest constitutive levels of BAFF; other myeloid subsets, including conventional dendritic cells (cDCs) and monocyte (MO) subsets, expressed lower levels. Treatment of BAFF-RFP mice with polyinosinic:polycytidylic acid increased BAFF expression in splenic Ly6Chi inflammatory MOs, CD11bhi activated NK subset, and in bone marrow myeloid precursors. Postinfection with West Nile virus (WNV), BAFF increased in CD8− cDCs and Nphs, and BAFF+ CD11bhi NK cells expanded in draining lymph nodes. The cell- and tissue-specific increases in BAFF expression were dependent on type I IFN signaling. MAVS also was required or contributed to BAFF expression in dendritic cell and MO subsets, respectively. Mice with deletion of Baff in either cDCs or Nphs had reduced Ab responses after NP-Ficoll immunization; thus, BAFF produced by both cDCs and Nphs contributes to T cell–independent Ab responses. Conversely, mice with a cDC Baff deficiency had increased mortality after WNV infection and decreased WNV-specific IgG and neutralizing Ab responses. BAFF produced by Nphs and cDCs is regulated differently and has key roles in Ab responses and protective immunity.

中文翻译：

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中性粒细胞和树突状细胞产生的 BAFF 受到不同的调控，在抗体反应和对西尼罗河病毒的保护性免疫中具有不同的作用

要点 BAFF 以细胞和组织特异性方式增加骨髓亚群。中性粒细胞和 DC BAFF 是最佳的不依赖于 T 细胞的 2 体液反应所必需的。DC 产生的 BAFF 是对西尼罗河病毒的保护性免疫所必需的。B 细胞激活因子 (BAFF) 是 B 细胞发育和响应 Ags 所必需的。BAFF 的失调会导致某些自身免疫性疾病和恶性肿瘤的发生。关于 BAFF 何时、何地、如何在体内产生，以及哪些 BAFF 产生细胞有助于 B 细胞反应，我们知之甚少。为了更好地了解 BAFF 功能，我们创建了 BAFF 报告基因 (BAFF-RFP) 小鼠和 Baff floxed (Bafffl/fl) 小鼠。来自 BAFF-RFP 小鼠的脾脏和骨髓中性粒细胞 (Nphs) 表达了最高的 BAFF 组成水平；其他髓系亚群，包括常规树突状细胞 (cDC) 和单核细胞 (MO) 亚群，表达水平较低。用聚肌苷：聚胞苷酸处理 BAFF-RFP 小鼠增加了脾脏 Ly6Chi 炎症 MO、CD11bhi 激活的 NK 亚群和骨髓髓样前体中 BAFF 的表达。西尼罗河病毒 (WNV) 感染后，CD8-cDCs 和 Nphs 中的 BAFF 增加，而 BAFF+ CD11bhi NK 细胞在引流淋巴结中扩增。BAFF 表达的细胞和组织特异性增加取决于 I 型干扰素信号。MAVS 也分别需要或有助于树突细胞和 MO 亚群中的 BAFF 表达。在 cDCs 或 Nphs 中缺失 Baff 的小鼠在 NP-Ficoll 免疫后抗体反应降低；因此，cDCs 和 Nphs 产生的 BAFF 有助于不依赖于 T 细胞的 Ab 反应。反过来，具有 cDC Baff 缺陷的小鼠在 WNV 感染后死亡率增加，并降低了 WNV 特异性 IgG 和中和抗体反应。由 Nphs 和 cDCs 产生的 BAFF 受到不同的调节，并且在 Ab 反应和保护性免疫中具有关键作用。