Memory B Cells with cross-reactive Abs to fluA(H1-H3)

To understand how the humoral immune system generates and matures protective responses to influenza virus infections and vaccinations. The group isolated B membory single cell clones from three unrelated, adult donors post TIV-vaccination, characterized the cross-reacting Abs to fluA (H1-H3) antigens, and generated the VDJ lineage tree of Bmem clones from one donor. The lineage and crystal structure analysis showed that members of a lineage 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 (HCDR3). Affinities of the clonal-lineage BCRs for historical influenza-virus HAs from both group 1 (H1) and group 2 (H3) viruses suggested that serial responses to seasonal influenza exposures had elicited the lineage and driven affinity maturation.