Discrimination of GC-dependent and -independent B-cell maturation pathways based on quantitative analysis of the replication history and SHM levels. (A) Replication history of 2 naive and 6 memory B-cell subsets as measured with the KREC assay.18 Three different levels of extensive proliferation in memory B-cell subsets in contrast to naive B cells (blue) could be identified: lower than GC (yellow bars), similar to GC (orange bars) and increased compared with GC (red bars). Bars represent mean values with SEM. In the whole figure, dashed and dotted lines represent values for centroblasts and centrocytes, respectively. Differences between each memory B-cell subset compared with centrocytes were statistically analyzed with the Mann-Whitney test. (B) Frequency of mutated nucleotides in rearranged IGHV genes. All individual data points are shown as gray dots, with red lines indicating the median value. Differences between each memory B-cell subset compared with centrocytes were statistically analyzed with the Mann-Whitney test. **P < .01, ***P < .001. (C) Frequency of mutated IGKV3-20 genes as measured with the IgκREHMA assay. Bars represent mean values with SEM. Differences between each memory B-cell subset compared with centrocytes were statistically analyzed with the Mann-Whitney test. *P < .05.
