Fig. 6: BCR repertoire of individuals deficient in CBL reveals a defect in immunoglobulin V gene usage and somatic hypermutation.
a,b, Usage of the top three IGHV IGHV4-34, IGHV4-59 and IGHV3-23 gene elements (a) and Ig JH4 and JH6 elements (b) in transitional, naive and memory B cells isolated from HDs and the indicated individuals deficient in CBL. c,d, CDR3 lengths in transitional, naive and memory cells isolated from HDs and individuals deficient in CBL (c) or CD10+CD20dim HSPC-derived B cell progenitors edited at the AAVS1 or CBL locus (d). aa, amino acids; Trans, transitional. e, Frequency of Ig somatic hypermutations (SHM) in memory B cells defined by the expression of distinct class-switched Ig isotypes. f, Frequency of clones with different levels of somatic hypermutation within IgM+ memory B cells. g, CDR replacement:silent (R:S) ratios in IgM, IgG and IgA memory B cells. Statistical significance was assessed with a Wilcoxon test with Bonferroni correction for multiple testing (if needed; b–d and g) or Dunn’s test for multiple comparisons (e and f); *P < 0.05. Data shown were generated from BCR sequencing of HDs (n = 5) and individuals with CBL-LOH (n = 5). Boxes and whiskers indicate the median (center line), quartiles (box) and data range within 1.5× interquartile range (whiskers), and dots show data values beyond 1.5× interquartile range. All individual data points are shown.
