N. Inoue et al., Restricted V-H gene usage in lamina propria B cells producing anticolon antibody from patients with ulcerative colitis, GASTROENTY, 121(1), 2001, pp. 15-23
Background & Aims: Autoimmune responses against colonic epithelium may play
a role in the development of colonic inflammation associated with ulcerati
ve colitis (UC). In this study, we established and characterized B-cell lin
es and clones that produced anticolon antibody from inflamed colonic mucosa
of UC subjects. Methods: B-cell lines were generated through Epstein-Barr
virus transformation of lamina propria lymphocytes (LPLs) from colonic muco
sa and peripheral blood lymphocytes, and these lines were screened for the
production of anticolon antibodies. B-cell lines were then cloned by limiti
ng dilution culture, and messenger RNA expression of immunoglobulin heavy-c
hain variable region (V-H) was assessed. Results:V-H gene families used in
B-cell lines established from LPLs of normal controls were diverse, and B-c
ell lines from UC LPLs expressed a restricted V(H)3 family usage. All 15 cl
ones from UC used a restricted VH3 gene family, whereas diverse V-H gene fa
milies were used by 24 clones from normal controls. The analysis of nucleot
ide sequences indicated that these clones were derived from various germlin
e gene segments. Conclusions: The restricted V-H gene usage in anticolon au
toantibodies producing B-cell clones suggests that a particular antigenic s
timulus contributes to the pathogenesis of UC.