Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are Abundant in Adult Human Repertoires.

Publication Type:

Journal Article

Authors:

McCarthy, Kevin R; Watanabe, Akiko; Kuraoka, Masayuki; Do, Khoi T; McGee, Charles E; Sempowski, Gregory D; Kepler, Thomas B; Schmidt, Aaron G; Kelsoe, Garnett; Harrison, Stephen C

Source:

Immunity, Volume 48, Issue 1, p.174-184.e9 (2018)

Keywords:

Adult, Antibodies, Viral, B-Lymphocytes, Cell Culture Techniques, Cross Reactions, Female, Flow Cytometry, Hemagglutinins, Viral, Humans, Influenza A virus, Interferometry, Male

Abstract:

<p>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.</p>

PDB: 
5W08 and 5W0D
Detector: 
PILATUS
Beamline: 
24-ID-C