Antibody responses to influenza vaccines tend to be focused on epitopes encountered during prior influenza exposures, with little production of de novo responses to novel epitopes. To examine the contribution of circulating antibody to this phenomenon, we passively transferred a hemagglutinin (HA)-specific monoclonal antibody (mAb) into mice before immunizing with whole inactivated virions. The HA mAb inhibited de novo HA-specific antibodies, plasmablasts, germinal center B cells, and memory B cells, while responses to a second antigen in the vaccine, neuraminidase (NA), were uninhibited. The HA mAb potently inhibited de novo antibody responses against epitopes near the HA mAb binding site. The HA mAb also promoted IgG1 class switching, an effect that, unlike the inhibition of HA responses, relied on signaling through Fc-gamma receptors. These studies suggest that circulating antibodies inhibit de novo B cell responses in an antigen-specific manner, which likely contributes to differences in antibody specificities elicited during primary and secondary influenza virus exposures.

中文翻译：

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流感病毒抗体抑制小鼠体内抗原特异性从头 B 细胞反应

对流感疫苗的抗体反应往往集中在先前流感暴露期间遇到的表位，而很少产生对新表位的从头反应。为了检查循环抗体对这种现象的影响，我们在用完整灭活病毒粒子进行免疫之前，将血凝素（HA）特异性单克隆抗体（mAb）被动转移到小鼠体内。 HA mAb 从头抑制 HA 特异性抗体、浆母细胞、生发中心 B 细胞和记忆 B 细胞，而对疫苗中第二种抗原神经氨酸酶 (NA) 的反应则不受抑制。 HA mAb 有效抑制针对 HA mAb 结合位点附近表位的从头抗体反应。 HA mAb 还促进 IgG1 类别转换，与抑制 HA 反应不同，这种作用依赖于 Fc-gamma 受体的信号传导。这些研究表明，循环抗体以抗原特异性方式抑制从头 B 细胞反应，这可能导致初次和继发性流感病毒暴露期间引起的抗体特异性差异。