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. 2012 Nov 19;122(12):4533–4543. doi: 10.1172/JCI63842

Figure 2. In MS, B cell receptors are subject to extensive intrathecal SHM.

Figure 2

Nucleotide sequences, represented by clusters shown in Figure 1, were selected from the IgG-VH sequence database and used to generate lineage trees using IgTree software (see Methods). (A–E) Representative trees for CSF-restricted clusters for patients (A) MS-1, (B) MS-3, (C) MS-4, (D) MS-6, and (E) MS-5. The corresponding IGHV, IGHJ, and most common H-CDR3 AA sequences are listed in Supplemental Table 2. In the lineage trees, each round node represents at least one unique IgG-VH sequence ranging from at least the 5′ end of H-CDR1 to the 3′ end of H-CDR3; larger nodes represent up to hundreds of identical sequences. Putative germline sequences were determined using SoDA ( https://dulci.org/soda/; ref. 36) and are labeled as black, and hypothetical intermediates calculated by IgTree are labeled as beige. The numbers represent mutational steps between nodes; only mutational steps >1 are indicated; thus, unlabeled branches represent a single mutation. Triangular nodes contain 2 or more singleton sequences in leaves.