title: Effect of environmental antigens on the Ig diversification and the selection of productive V-J joints in the bursa.
abstract: In chickens, a single set of unique functional segments of both Ig H and L chain genes is rearranged during early embryogenesis to generate a pool of B cell progenitors that will be diversified in the bursa by gene conversion, forming the preimmune repertoire. After hatching, bursal cells are exposed to environmental Ags in the bursal lumen. We prepared B cells from each single bursal follicle and used PCR-directed Ig L chain gene analysis to study the differentiation of B cells and the effect of antigenic stimulation from the bursal lumen on the neonatal chicken B cell repertoire formation. Selective amplification of B cell clones with a productive V-J joint was observed during the late embryonic stage, possibly by the interaction with ligands expressed on the bursal stroma and further accelerated in the neonatal chicken. Administration of the artificial Ags into the bursal lumen before the isolation of bursa by bursal duct ligation in the embryo caused a significant increase in lymphocytes with a productive V-J joint in the neonatal chicken bursa compared with the isolated bursa. Intra- and interclonal diversity of a complementarity-determining region measured by an evolutionary distance increased during bursal development. Clonal diversification did not require stimulation by artificial Ags from the bursal lumen. Thus, the preimmune repertoire in the bursa is generated by gene conversion during Ag-independent B cell proliferation, and antigenic stimulation from the bursal epithelium to bursal B cells plays roles in the selection of clones with a productive V-J joint.
authors.affiliation: Department of Biophysics, Graduate School of Science, Center for Molecular Biology and Genetics, Kyoto University, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arakawa
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Kuma
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yasuda
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ekino
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Hideo
authors.initials: H
authors.lastname: Yamagishi
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000818:Animals; D000916:Antibody Diversity / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002060:Bursa of Fabricius / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002645:Chickens / Q000254:growth & development / Q000276:immunology*; D002999:Clone Cells; D003001:Cloning, Molecular; D022801:Complementarity Determining Regions / Q000096:biosynthesis / Q000235:genetics; D019143:Evolution, Molecular; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D018095:Germ-Line Mutation; D007133:Immunoglobulin Joining Region / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009596:Nitrophenols / Q000276:immunology / Q000494:pharmacology; D010648:Phenylacetates
chemical_list: D022801:Complementarity Determining Regions; D007133:Immunoglobulin Joining Region; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid