背景:B细胞对于提供针对急性甲型流感病毒(IAV)感染的体液保护至关重要。FcγRIIB,抗体(Ab)生产的调节剂,影响病原体感染期间的免疫反应,但其对体液保护和B细胞介导的抗IAV反应的具体影响尚不清楚。
方法:为了研究FcγRIIB在急性IAV感染期间宿主防御和B细胞功能中的作用,我们产生了全身性FcγRIIB缺乏的小鼠,功能损害,和B细胞特异性FcγRIIB缺失。我们用PR8(H1N1)或Hkx31(H3N2)IAV感染这些小鼠,并评估体重保存,存活率,Ab生产,病毒中和,Ab亲和力成熟,和生发中心B细胞发育。
结果:缺乏FcγRIIB或功能受损的小鼠表现出改善的保护作用,保持体重,并在IAV感染期间增加存活率。值得注意的是,单倍体不足FcγRIIB功能的小鼠表现出保护作用。B细胞中FcγRIIB的选择性缺乏导致Ab产生增强,导致血清中IAV特异性Abs升高,具有优异的病毒中和效力。然而,对病毒特异性抗体亲和力成熟指数的影响不大。因此,FcγRIIB缺陷B细胞在IAV感染期间维持正常的生发中心B细胞发育,而野生型小鼠表现出延迟分化。
结论:我们的研究强调了FcγRIIB在急性IAV感染期间宿主防御和B细胞介导的免疫中的关键作用。此外,我们的发现对抗病毒治疗有意义,特别是在IAV感染的初始阶段,旨在增强宿主的体液免疫反应。
BACKGROUND: B cells are essential for providing humoral protection against acute influenza A virus (IAV) infection.
FcγRIIB, a regulator of antibody (Ab) production, influences immune responses during pathogen infections, but its specific impact on humoral protection and B cell-mediated responses against IAV remains unclear.
METHODS: To investigate
FcγRIIB\'s role in host defense and B cell function during acute IAV infection, we generated mice with systemic
FcγRIIB deficiency, functional impairment, and B cell-specific
FcγRIIB deletion. We infected these mice with PR8 (H1N1) or Hkx31 (H3N2) IAVs and evaluated body weight preservation, survival rates, Ab production, viral neutralization, Ab affinity maturation, and germinal center B cell development.
RESULTS: Mice lacking FcγRIIB or with impaired function showed improved protection, preserved body weight, and increased survival rates during IAV infection. Notably, mice with haploinsufficient
FcγRIIB function displayed protective effects. Selective deficiency of FcγRIIB in B cells led to enhanced Ab production, resulting in elevated IAV-specific Abs in the serum with superior viral neutralizing potency. However, the impact on the affinity maturation index of virus-specific Abs was modest. Accordingly, FcγRIIB-deficient B cells maintained normal germinal center B cell development during IAV infection, whereas wild-type mice exhibited delayed differentiation.
CONCLUSIONS: Our research underscores the pivotal role of FcγRIIB in host defense and B cell-mediated immunity during acute IAV infection. Additionally, our discoveries hold implications for antiviral treatments, particularly during the initial stages of IAV infection, aimed at enhancing the host\'s humoral immune response.