a, The maximum clone sizes (as a percentage of unique VDJ sequences of a given isotype in the largest clone divided by the total number of unique BCRs of that isotype) for BCR repertoires from PBMCs per disease across isotypes. For box plots, box lines show the 25th, 50th and 75th percentiles; whiskers show the upper and lower quartiles. b, Global repertoire dissimilarity measures between disease groups. Heat map showing the global repertoire dissimilarity measures between disease groups on the basis of a combination of three main BCR features (isotype frequency, clonal expansion index and clonal diversification index) and determining joint differences between groups (MANOVA test using disease group and age as covariables). The light and dark orange squares indicate significant differences between corresponding disease groups (FDR < 0.05 and FDR < 0.005, respectively, determined by Šidák method). n = 32 for healthy individuals and n = 20, n = 34, n = 12, n = 10, n = 23, n = 10 and n = 13 for patients with AAV (MPO+), AAV (PR3+), EGPA, SLE, Crohn’s disease, IgAV and Behçet’s disease, respectively. c, The sequence of B cell isotype expression is defined by the order of constant regions on the chromosome. Possible class-switching events are depicted by the arrows between constant regions. d, Schematic diagram of class-switching types that are detectable from the sequencing data. The differences from c are a result of the ambiguity of isotype between IgA1 and IgA2, and IgG1 and IgG2, in the isotype-specific sequencing, and splicing of IgD from IgM-containing transcripts. Possible class-switching events are represented by the arrows between constant regions. e, Several unique RNA sequences with identical antigen-binding regions (V–D–J) but different constant regions represent instances of class switching. f, Schematic diagram of the subsampling of BCR repertoires to generate the relative class-switch event frequency. This is the frequency of unique VDJ regions that are expressed as two isotypes (that is, from more than one B cell, one of which has undergone CSR), and determined as the proportion of unique BCRs that are present as both isotypes (IgX and IgY) within a random subsample of 8,000 BCRs, from which the mean of 1,000 repeats was generated. This provides information on the frequency of BCRs that are observed to be associated with any two isotypes (class-switching events), and accounts for total read depth, but not for differences in the relative frequencies of BCRs per isotype. For a, n = 32 for healthy individuals and n = 54, n = 12, n = 10, n = 23, n = 10 and n = 13 for patients with AAV, EGPA, SLE, Crohn’s disease, IgAV and Behçet’s disease, respectively. P values were calculated by two-way ANOVA, *FDR < 0.05, **FDR < 0.005, ***FDR < 0.0005 (determined by the Šidák method).