title: Activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen and is associated with expansion of the primary antibody repertoire in the absence of exogenous antigens.
abstract: Due to a limited range of immunoglobulin (Ig) genes, cattle and several other domestic animals rely on postrecombinatorial amplification of the primary repertoire. We report that activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen but not in fetal bone marrow. The numbers of IGHV (immunoglobulin heavy chain variable) mutations correlate with AID expression. The mutational profile in the fetuses is similar to postnatal and immunized calves, with targeting of complementarity-determining region (CDR) over framework region (FR), preference of replacement over silent mutations in CDRs but not in FRs, and targeting of the AID hotspot motif RGYW/WRCY. Statistical analysis indicates negative selection on FRs and positive selection on CDRs. Our results suggest that AID-mediated somatic hypermutation and selection take place in bovine fetuses, implying a role for AID in the diversification of the primary antibody repertoire in the absence of exogenous antigens.
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Liljavirta
authors.forename: A
authors.initials: A
authors.lastname: Ekman
authors.forename: J S
authors.initials: JS
authors.lastname: Knight
authors.forename: A
authors.initials: A
authors.lastname: Pernthaner
authors.forename: A
authors.initials: A
authors.lastname: Iivanainen
authors.forename: M
authors.initials: M
authors.lastname: Niku
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D000916:Antibody Diversity / Q000235:genetics; D000917:Antibody Formation / Q000235:genetics; D002417:Cattle; D060966:Clonal Selection, Antigen-Mediated; D022801:Complementarity Determining Regions / Q000235:genetics; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D005333:Fetus; D007082:Ileum / Q000166:cytology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010581:Peyer's Patches / Q000378:metabolism*; D027041:Somatic Hypermutation, Immunoglobulin; D013154:Spleen / Q000378:metabolism*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase