Article ; Online: The proximal J kappa germline-transcript promoter facilitates receptor editing through control of ordered recombination.
PloS one
2015 Volume 10, Issue 1, Page(s) e0113824
Abstract: V(D)J recombination creates antibody light chain diversity by joining a Vκ gene segment with one of four Jκ segments. Two Jκ germline-transcript (GT) promoters control Vκ-Jκ joining, but the mechanisms that govern Jκ choice are unclear. Here, we show in ... ...
| Abstract | V(D)J recombination creates antibody light chain diversity by joining a Vκ gene segment with one of four Jκ segments. Two Jκ germline-transcript (GT) promoters control Vκ-Jκ joining, but the mechanisms that govern Jκ choice are unclear. Here, we show in gene-targeted mice that the proximal GT promoter helps targeting rearrangements to Jκ1 by preventing premature DNA breaks at Jκ2. Consequently, cells lacking the proximal GT promoter show a biased utilization of downstream Jκ segments, resulting in a diminished potential for receptor editing. Surprisingly, the proximal--in contrast to the distal--GT promoter is transcriptionally inactive prior to Igκ recombination, indicating that its role in Jκ choice is independent of classical promoter function. Removal of the proximal GT promoter increases H3K4me3 levels at Jκ segments, suggesting that this promoter could act as a suppressor of recombination by limiting chromatin accessibility to RAG. Our findings identify the first cis-element critical for Jκ choice and demonstrate that ordered Igκ recombination facilitates receptor editing. |
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| MeSH term(s) | Animals ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Cells, Cultured ; Female ; Flow Cytometry ; Gene Expression/immunology ; Germ Cells/immunology ; Germ Cells/metabolism ; Histones/immunology ; Histones/metabolism ; Immunoglobulin Joining Region/genetics ; Immunoglobulin Joining Region/immunology ; Immunoglobulin Variable Region/genetics ; Immunoglobulin Variable Region/immunology ; Immunoglobulin kappa-Chains/genetics ; Immunoglobulin kappa-Chains/immunology ; Lysine/immunology ; Lysine/metabolism ; Male ; Methylation ; Mice, Inbred C57BL ; Mice, Knockout ; Promoter Regions, Genetic/genetics ; Promoter Regions, Genetic/immunology ; Receptors, Antigen, B-Cell/genetics ; Receptors, Antigen, B-Cell/immunology ; Reverse Transcriptase Polymerase Chain Reaction ; V(D)J Recombination/genetics ; V(D)J Recombination/immunology |
| Chemical Substances | Histones ; Immunoglobulin Joining Region ; Immunoglobulin Variable Region ; Immunoglobulin kappa-Chains ; Receptors, Antigen, B-Cell ; Lysine (K3Z4F929H6) |
| Language | English |
| Publishing date | 2015-01-05 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ISSN | 1932-6203 |
| ISSN (online) | 1932-6203 |
| DOI | 10.1371/journal.pone.0113824 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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