Receptor editing constrains development of phosphatidyl choline-specific B cells in V(H)12-transgenic mice

B1 B cells reactive to phosphatidyl choline (PtC) exhibit restricted immunoglobulin heavy chain (HC) and light chain (LC) combinations, exemplified by V(H)12/Vκ4/5H. Two checkpoints are thought to focus PtC(+) B cell maturation in V(H)12-transgenic mice (VH12 mice): V-J rearrangements encoding a “permissive” LC capable of V(H)12 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.