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Memory B cells that cross-react with group 1 and group 2 influenza A viruses are abundant in adult human repertoires
McCarthy, K. R., Watanabe, A., Kuraoka, M., Do, K. T., McGee, C. E., Sempowski, G. D., Kepler, T. B., Schmidt, A. G., Kelsoe, G., & Harrison, S. C. (2018). Memory B cells that cross-react with group 1 and group 2 influenza A viruses are abundant in adult human repertoires. Immunity, 48(1), 174-184.e9. https://doi.org/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.
