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

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2018 Jan 19

PMID 29343437

Citations 89

Authors

Kevin R McCarthy

Akiko Watanabe

Masayuki Kuraoka

Khoi T Do

Charles E McGee

Gregory D Sempowski

Thomas B Kepler

Aaron G Schmidt

Garnett Kelsoe

Stephen C Harrison

Affiliations

Soon will be listed here.

Abstract

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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