B cells selected for apoptosis in the sheep ileal Peyer's patch have enhanced mutational diversity in the Ig V lambda light chain
Maybaum, T.A.; Reynolds, J.D.
Journal of Immunology 157(4): 1474-1484
1996
ISSN/ISBN: 0022-1767 PMID: 8759728 Document Number: 463090
To investigate the molecular events associated with B cell apoptosis, follicular B cells from the large Peyer's patch (PP) in the ileum of 8- to 10-week-old sheep were analysed. Ig V lambda sequences from apoptotic B cells were compared with sequences from B cells about to emigrate from the PP. The sequences originated from two germ line genes, V lambda 5.1 and V lambda 5.3. Only V lambda 5.1 was rearranged in apoptotic cells, whereas both V lambda 5.1 and V lambda 5.3 were rearranged in B cells about to emigrate. Apoptotic B cells had evidence of increased Ig sequence diversity based on: significantly greater replacement to silent mutation ratios in the complementarity determining regions; the more random distribution of mutations; and the lack of mutational specificity compared with the mutational bias favouring transitions and purines in B cells about to emigrate. It is suggested that the continual proliferation of B cells in the PP follicle may increase their affinity to local antigens (Ags) and that the Ags that are sequestered in this environment may stimulate the production of B cells with such high-affinity receptors that ligation would trigger apoptosis. This could account for the deletion of B cells with specificity for self-antigens, selecting ligands as well as gut-derived food and microbial Ags. This process could contribute to the elimination of self-reactive B cells, the expansion of the antibody repertoire, and the generation of oral tolerance. It is concluded that the sIg receptor may play a critical role in mediating B cell selection in the sheep ileal PP.