Immunity
Volume 48, Issue 1, 16 January 2018, Pages 174-184.e9
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Article
Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are Abundant in Adult Human Repertoires

https://doi.org/10.1016/j.immuni.2017.12.009Get rights and content
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Highlights

  • Human Bmem cells were found with BCRs cross-reactive for influenza A groups 1 and 2

  • Cross-group Bmem cells were abundant, unlike cross-group serum antibodies

  • Structures of HA receptor-site directed, cross-group antibodies showed key contacts

  • Cross-group lineage antibodies were similar to a genetically unrelated antibody

Summary

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.

Keywords

convergent evolution
B cell repertoire
clonal selection
influenza hemagglutinin

Cited by (0)

6

Present address: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA

7

Contributed equally