title: Class-Switch Recombination in the Absence of the IgH 3' Regulatory Region.
abstract: The ∼28-kb 3' regulatory region (3'RR), which is located at the most distal 3' region of the Ig H chain locus, has multiple regulatory functions that control IgH expression, class-switch recombination (CSR), and somatic hypermutation. In this article, we report that deletion of the entire 3'RR in a mouse B cell line that is capable of robust cytokine-dependent CSR to IgA results in reduced, but not abolished, CSR. These data suggest that 3'RR is not absolutely required for CSR and, thus, is not essential for targeting activation-induced cytidine deaminase to S regions, as was suggested. Moreover, replacing 3'RR with a DNA fragment including only its four DNase I hypersensitive sites (lacking the large spacer regions) restores CSR to a level equivalent to or even higher than in wild-type cells, suggesting that the four hypersensitive sites contain most of the CSR-promoting functions of 3'RR. Stimulated cells express abundant germline transcripts, with the presence or absence of 3'RR, providing evidence that 3'RR has a role in promoting CSR that is unique from enhancing S region transcription.
authors: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824;
authors: Ahrom
authors: A
authors: Kim
authors: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824;
authors: Li
authors: L
authors: Han
authors: Department of Medicine, Division of Hematology-Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136; and.
authors: Gabriel E
authors: GE
authors: Santiago
authors: Department of Medicine, Division of Hematology-Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136; and Geriatric Research, Education, and Clinical Center, Miami Veterans Affairs Healthcare System, Miami, FL 33125.
authors: Ramiro E
authors: RE
authors: Verdun
authors: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824; yuke@msu.edu.
authors: Kefei
authors: 0000-0002-3870-2812
authors: K
authors: Yu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007074:Immunoglobulin G / Q000235:genetics* / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D007134:Immunoglobulin Switch Region / Q000235:genetics* / Q000276:immunology; D051379:Mice
chemical_list: D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains