ArticleProceedings of the National Academy of Sciences of the United States of America2014
Zinc-finger protein ZFP318 is essential for expression of IgD, the alternatively spliced Igh product made by mature B lymphocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 59 citations in OpenAlex.
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- Biophysical properties of IgD determine thresholds for self-tolerance and selection into germinal centers.bioRxiv : the preprint server for biology · 2026Article
- The emerging roles of alternative splicing in modulating tumor immune responses and immunotherapies.Cell death and differentiation · 2026Review
- Abnormal immunoglobulin expression and B-cell follicle organization in inborn errors of immunity/primary immunodeficiency.Virchows Archiv : an international journal of pathology · 2026Article
- RNA-binding proteins and ribonucleoproteins as determinants of immunity.Nature reviews. Immunology · 2026Review
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- Systems genetics uncover new loci containing functional gene candidates in Mycobacterium tuberculosis-infected Diversity Outbred mice.PLoS pathogens · 2024Article
- Central tolerance shapes the neutralizing B cell repertoire against a persisting virus in its natural host.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Exploring Immune Cell Diversity in the Lacrimal Glands of Healthy Mice: A Single-Cell RNA-Sequencing Atlas.International journal of molecular sciences · 2024Article
- Systems genetics uncover new loci containing functional gene candidates inbioRxiv : the preprint server for biology · 2023Article
- IgD shapes the pre-immune naïve B cell compartment in humans.Frontiers in immunology · 2023Article
- Host and Viral Zinc-Finger Proteins in COVID-19.International journal of molecular sciences · 2022Review
- Rad52 mediates class-switch DNA recombination to IgD.Nature communications · 2022Article
- Human marginal zone B cell development from early T2 progenitors.The Journal of experimental medicine · 2021Article
- Immunoglobulin expression and the humoral immune response is regulated by the non-canonical poly(A) polymerase TENT5C.Nature communications · 2020Article
- Teleost IgDCell reports · 2019Article
- Self-reactivity on a spectrum: A sliding scale of peripheral B cell tolerance.Immunological reviews · 2019Review
- Ikaros prevents autoimmunity by controlling anergy and Toll-like receptor signaling in B cells.Nature immunology · 2019Article
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
IgD and IgM are produced by alternative splicing of long primary RNA transcripts from the Ig heavy chain (Igh) locus and serve as the receptors for antigen on naïve mature B lymphocytes. IgM is made selectively in immature B cells, whereas IgD is coexpressed with IgM when the cells mature into follicular or marginal zone B cells, but the transacting factors responsible for this regulated change in splicing have remained elusive. Here, we use a genetic screen in mice to identify ZFP318, a nuclear protein with two U1-type zinc fingers found in RNA-binding proteins and no known role in the immune system, as a critical factor for IgD expression. A point mutation in an evolutionarily conserved lysine-rich domain encoded by the alternatively spliced Zfp318 exon 10 abolished IgD expression on marginal zone B cells, decreased IgD on follicular B cells, and increased IgM, but only slightly decreased the percentage of B cells and did not decrease expression of other maturation markers CD21, CD23, or CD62L. A targeted Zfp318 null allele extinguished IgD expression on mature B cells and increased IgM. Zfp318 mRNA is developmentally regulated in parallel with IgD, with little in pro-B cells, moderate amounts in immature B cells, and high levels selectively in mature follicular B cells. These findings identify ZFP318 as a crucial factor regulating the expression of the two major antibody isotypes on the surface of most mature B cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.