| First Author | Worth AN | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 11 | Pages | 110899 |
| PubMed ID | 35705027 | Mgi Jnum | J:337374 |
| Mgi Id | MGI:7311483 | Doi | 10.1016/j.celrep.2022.110899 |
| Citation | Worth AN, et al. (2022) Receptor editing constrains development of phosphatidyl choline-specific B cells in VH12-transgenic mice. Cell Rep 39(11):110899 |
| abstractText | B1 B cells reactive to phosphatidyl choline (PtC) exhibit restricted immunoglobulin heavy chain (HC) and light chain (LC) combinations, exemplified by VH12/Vkappa4/5H. Two checkpoints are thought to focus PtC(+) B cell maturation in VH12-transgenic mice (VH12 mice): V-J rearrangements encoding a "permissive" LC capable of VH12 HC pairing are selected first, followed by positive selection based on PtC binding, often requiring LC receptor editing to salvage PtC(-) B cells and acquire PtC reactivity. However, evidence obtained from breeding VH12 mice to editing-defective dnRAG1 mice and analyzing LC sequences from PtC(+) and PtC(-) B cell subsets instead suggests that receptor editing functions after initial positive selection to remove PtC(+) B cells in VH12 mice. This offers a mechanism to constrain natural, polyreactive B cells to limit their frequency. Sequencing also reveals occasional in-frame hybrid LC genes, reminiscent of type 2 gene replacement, that, testing suggests, arise via a recombination-activating gene (RAG)-independent mechanism. |
