Biased J(H) usage in plasma cell immunoglobulin gene sequences from colonic mucosa in ulcerative colitis but not in Crohn's disease

Background-Ulcerative colitis is an inflammatory disease of the colonic and rectal mucosa. Autoantibodies have been observed in ulcerative colitis whi ch may have a role in the pathogenesis of the disease. Evidence also sugges ts that there is an hereditary predisposition towards the disease, although no individual genes have been identified. Aims-This is a pilot study of immunoglobulin heavy chain genes (IgH) in ulc erative colitis to determine whether they have any particular genetic chara cteristics which may lead to a better understanding of the disease aetiolog y. Subjects-Colonic or rectal tissue was obtained from five children with ulce rative colitis. Tissue was also obtained from five children with Crohn's di sease and five children who did not have inflammatory bowel disease as cont rols. Methods-B cells and IgD+ B cells were identified by immunohistochemistry on frozen sections. Areas of lamina propria containing plasma cells, and area s of IgD+ B cells were microdissected. The immunoglobulin genes were PCR am plified, cloned, and sequenced. Sequences were analysed for content of soma tic mutations and composition of heavy chain. Results-An increase in the use of J(H)6 and DXP'1, and a decrease in the us e of J(H)4, gene segments in immunoglobulin genes fi om lamina propria plas ma cells, and from virgin IgD+ B cells, was found in patients with ulcerati ve colitis. These biases were not present in the control groups. Conclusions-There is a fundamental difference in the immunoglobulin genes f rom patients with ulcerative colitis. Whether this is caused by a differenc e in content of immunoglobulin gene segments in the germline or a differenc e in the recombination mechanism is not known.