Journal
IMMUNITY
Volume 48, Issue 1, Pages 174-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2017.12.009
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Funding
- National Institutes of Health and National Institute of Allergy and Infectious Diseases [UC6-AI058607]
- NIH [P41 GM103403, P01 AI089618, U19 AI117892, R01 AI128832]
- Pilatus 6M detector on 24-ID-C by NIHORIP HEI grant [S10-RR029205]
- DOE Office of Science by Argonne National Laboratory [DE-AC02-06CH11357]
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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.
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