Fig. 2: THX mice huBCR repertoire and clonality are similar to those in humans. | Nature Immunology

Fig. 2: THX mice huBCR repertoire and clonality are similar to those in humans.

From: A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses

Fig. 2

a, huIgH VH, D and JH gene genomic representation and expression in blood and spleen huIgM+ B cells of healthy humans (n = 3, HS 01, 02, 03) and non-intentionally immunized THX mice (n = 3, THX 365, 366, 367), depicted as stacked columns. In these, different colors denote different huVH, huD or huJH gene families; color gradients denote individual family members—the huIgH locus haploid complement consists of 36–49 functional huVH genes segregated into 7 families32. b, Heat map of individual huVH family members in huIgM+ B cells of HS and THX mice as in a. c, Associated expression of huVH and huJH genes in huIgM+ B cell repertoire of HS and THX mice as in a, depicted by Circos plots. Outermost Circos plot tracks mark the boundaries of each huVH or huJH region subfamily. d, huIgH CDR3 (translated amino acid sequence) length distribution (left) and frequency (right) in huIgM+ B cell recombined huVHDJH-Cμ transcripts of HS and THX mice as in a—the somatically generated IgH CDR3 is the most polymorphic BCR region and provides the main structural correlate for antigen binding. In the violin plots, the upper and lower edges of the box plot indicate the 75th and 25th percentiles, respectively, and the middle line indicates the median. Each dot depicts CDR3 length in an individual huB cell. e, huB cell clones in HS and THX mice as in a, as identified by unique huVHDJH-Cμ (including CDR3 as translated amino acid sequence) transcripts and depicted by TreeMaps. Individual rectangle or square (unique color) area reflects huB cell clone size. In THX mice, huVHDJH-Cμ transcripts identified 521,859, 23,052 and 20,045 discrete huB cell clones in the same order of magnitude as in HS huVHDJH-Cμ transcripts, which identified 11,115, 9,016 and 11,570 huB cell clones. f, huIgK chain (Vκ and Jκ) and huIgL chain (Vλ and Jλ-Cλ) gene genomic representation and expression in huIgM+ B cells of HS and THX mice as in a, depicted as stacked columns. In these, different colors denote different huVκ, huJκ or huVλ, huCλ gene families; color gradients denote individual gene family members—the huIgκ locus comprises 39 functional huVκ genes and 5 huJκ genes, while the huIgλ locus comprises 30 functional huVλ genes segregated into 10 subgroups and 5 functional huJλ-Cλ clusters32.

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