Fig. 4. Longitudinal analysis of the 438-B11/D5 lineage development.

(A) Identity-divergence analysis of the unbiased heavy-chain (H) and light-chain (κ) repertoires of donor CBJC438 at time points 2005, 2008, and 2012. For the whole-repertoire analysis (rows 1 and 3), sequences are plotted as a function of sequence identity to 438-B11 and sequence divergence from putative germline genes. Color coding denotes sequence density. For analysis of the 438-B11–encoding germline gene families (rows 2 and 4), sequences are plotted as a function of sequence identity to 438-B11 and sequence divergence from IgHV1-69 and IgKV3-20 for the heavy and light chains, respectively. The germline gene family distribution is presented as black contour lines. 438-B11 and sequences identified on the basis of various criteria (see legend below figure) are shown on the black contours with the number of sequences labeled accordingly. (B) Dendrograms of functionally tested heavy and light chains are rooted by their respective germline allelic genes, IgHV1-69 and IgKV3-20, respectively. Heavy chains from 2005, 2008, and 2012 are presented in three separate dendrograms, while light chains from all three time points are shown in one dendrogram. (C) Neutralization breadth (%) and potency (μg/ml) of NGS-derived heavy and light chains paired with their respective 438-D5 partner chains on a global panel. The color-coding scheme is based on their potency.