Figure 1. Mucosal plasma cells comprise a single dominant population.
Charts illustrating the numbers of IGLV sequences (vertical axis) with different numbers of point mutations acquired by somatic hypermutation. Sequences are grouped on the horizontal axis as those with 0-4, 5-8, 9-12 etc mutations. Points represent the total number of sequences in the sampled population with the specified number of mutations. A. Mutations in rearrangements of IGLV1 and IGLV2 from plasma cells sampled from sections of ileal lamina propria from 3 individuals checked microscopically to be free of lymphoid tissue. B. Mutations in IGLV from single isolated colonic IgA+ plasma cells from 2 individuals. The distribution of mutations illustrated in A and B approximates to a single curve. C. Mutations in IGLV1 and IGLV2 used by IgA plasma cells from bone marrow from 3 individuals show 2 peaks in frequency of somatic hypermutation. D. Ratios of productive (white bar) to non-productive (black bar) rearrangements of IGLV1 and IGLV2. Sequences analysed were: BM<12 (IGLV1 and IGLV2 from bone marrow plasma cells with 12 mutations or fewer, as boxed in C), BM>12 (IGLV1 and IGLV2 from bone marrow plasma cells with more than 12 mutations as boxed in C), Gut (rearrangements of IGLV1 and IGLV2 from microdissected lamina propria cells shown in A) and Gut PCs (rearrangements of IGLV1 and IGLV2 from single isolated lamina propria plasma cells in B). Expected 71% in-frame is indicated with a dotted line. The ratio of in-frame: out of frame rearrangements of IGLV1 and IGLV2 in bone marrow plasma cells is not biased away from expected. However, there is a significant bias away from expected 71% in-frame rearrangements in the more mutated sequences from bone marrow, Gut and Gut PC groups (p=0.02, p<0.001 and p=0.01 respectively) and a significant difference between the more and less mutated subsets of IGLV1 and IGLV2 bone marrow plasma cells (p=0.03). E. Frequency of mutations in IGHV from blood-borne IgA+, α4β7hi cells from 3 individuals F. Mutations in IGHV from GC derived, blood-borne IgA+, α4β7hi B cells that bind CTB after an oral vaccination of 3 individuals with vaccine containing CTB display similar features to those from pre-immune blood not selected for any specificity.