Biased JH usage in plasma cell immunoglobulin gene sequences from colonic mucosa in ulcerative colitis but not in Crohn's disease

摘要

BACKGROUND—Ulcerativecolitis is an inflammatory disease of the colonic and rectal mucosa.Autoantibodies have been observed in ulcerative colitis which may havea role in the pathogenesis of the disease. Evidence also suggests thatthere is an hereditary predisposition towards the disease, although noindividual genes have been identified. 
AIMS—This is a pilotstudy of immunoglobulin heavy chain genes (IgH) in ulcerative colitisto determine whether they have any particular genetic characteristicswhich may lead to a better understanding of the disease aetiology. 
SUBJECTS—Colonic orrectal tissue was obtained from five children with ulcerative colitis.Tissue was also obtained from five children with Crohn's disease andfive children who did not have inflammatory bowel disease as controls. 
METHODS—B cells andIgD+ B cells were identified by immunohistochemistry on frozensections. Areas of lamina propria containing plasma cells, and areas ofIgD+ B cells were microdissected. The immunoglobulin genes were PCRamplified, cloned, and sequenced. Sequences were analysed for contentof somatic mutations and composition of heavy chain. 
RESULTS—Anincrease in the use of JH6 and DXP'1, and a decrease in theuse of JH4, gene segments in immunoglobulin genes fromlamina propria plasma cells, and from virgin IgD+ B cells, was found inpatients with ulcerative colitis. These biases were not present in thecontrol groups. 
CONCLUSIONS—There is afundamental difference in the immunoglobulin genes from patients withulcerative colitis. Whether this is caused by a difference in contentof immunoglobulin gene segments in the germline or a difference in therecombination mechanism is not known.