Human B cell antigen-receptor (BCR) repertoires reflect repeated exposures to evolving influenza viruses; new exposures update the previously generated B cell memory (Bmem) population. Despite structural similarity of hemagglutinins (HAs) from the two groups of influenza A viruses, cross-reacting antibodies (Abs) are uncommon. We analyzed Bmem compartments in three unrelated, adult donors and found frequent cross-group BCRs, both HA-head directed and non-head directed. Members of a clonal lineage from one donor had a BCR structure similar to that of a previously described Ab, encoded by different gene segments. Comparison showed that both Abs contacted the HA receptor-binding site through long heavy-chain third complementarity determining regions. Affinities of the clonal-lineage BCRs for historical influenza-virus HAs from both group 1 and group 2 viruses suggested that serial responses to seasonal influenza exposures had elicited the lineage and driven affinity maturation. We propose that appropriate immunization regimens might elicit a comparably broad response.

人类 B 细胞抗原受体 (BCR) 库反映了反复暴露于不断演变的流感病毒；新的曝光会更新先前生成的 B 细胞记忆 (Bmem) 群体。尽管来自两组甲型流感病毒的血凝素 (HAs) 结构相似，但交叉反应抗体 (Abs) 并不常见。我们分析了三个不相关的成年供体的 Bmem 隔间，发现了频繁的跨组 BCR，包括 HA 头部定向和非头部定向。来自一个供体的克隆谱系成员具有与先前描述的抗体相似的 BCR 结构，由不同的基因片段编码。比较表明，两种抗体都通过长重链第三互补决定区与 HA 受体结合位点接触。来自第 1 组和第 2 组病毒的历史流感病毒 HA 的克隆谱系 BCR 的亲和力表明，对季节性流感暴露的连续反应引发了谱系并推动了亲和力成熟。我们建议适当的免疫方案可能会引起相当广泛的反应。