Receptor editing constrains development of phosphatidyl choline-specific B cells in VH12-transgenic mice

Alexandra N. Worth, Victoria L. Palmer, N. Max Schabla, Greg A. Perry, Anna N. Fraser-Philbin, Patrick C. Swanson

Research output: Contribution to journalArticlepeer-review

Abstract

B1 B cells reactive to phosphatidyl choline (PtC) exhibit restricted immunoglobulin heavy chain (HC) and light chain (LC) combinations, exemplified by VH12/Vκ4/5H. 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.

Original languageEnglish (US)
Article number110899
JournalCell Reports
Volume39
Issue number11
DOIs
StatePublished - Jun 14 2022

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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