Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Department of Immunology, Duke University, Durham, North Carolina 27710, USA.
Immunity. 2018 Jan 16;48(1):174-184.e9. doi: 10.1016/j.immuni.2017.12.009.
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) 库反映了对不断进化的流感病毒的反复暴露；新的暴露会更新先前产生的 B 细胞记忆 (Bmem) 群体。尽管来自两组甲型流感病毒的血凝素 (HA) 具有结构相似性，但交叉反应抗体 (Abs) 并不常见。我们分析了三名无关的成年供体的 Bmem 隔室，发现了频繁的跨组 BCR，包括 HA 头部定向和非头部定向的 BCR。来自一个供体的一个克隆谱系的成员具有与先前描述的 Ab 相似的 BCR 结构，该 Ab 由不同的基因片段编码。比较表明，这两种 Abs 通过重链的长第三互补决定区接触到 HA 的受体结合位点。该克隆谱系 BCR 对来自 1 组和 2 组病毒的历史流感病毒 HA 的亲和力表明，对季节性流感暴露的连续反应引发了该谱系并驱动了亲和力成熟。我们提出，适当的免疫方案可能会引发类似的广泛反应。
