Zinc-finger protein ZFP318 is essential for expression of IgD, the alternatively spliced Igh product made by mature B lymphocytes

Anselm Enders; Alanna Short; Lisa A. MiosgeHannes BergmannYovina SontaniEdward M. BertramBelinda WhittleBhavani BalakishnanKaoru YoshidaGeoff SjollemMatthew A. FieldT. Daniel AndrewsHiromi HagiwaraChristopher C. Goodnow

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Zinc-finger protein ZFP318 is essential for expression of IgD, the alternatively spliced Igh product made by mature B lymphocytes

机译：Zinc-finger protein ZFP318 is essential for expression of IgD, the alternatively spliced Igh product made by mature B lymphocytes

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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 na?ve 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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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第12期|4513-4518|共6页
作者
Anselm Enders; Alanna Short; Lisa A. MiosgeHannes BergmannYovina SontaniEdward M. BertramBelinda WhittleBhavani BalakishnanKaoru YoshidaGeoff SjollemMatthew A. FieldT. Daniel AndrewsHiromi HagiwaraChristopher C. Goodnow;
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作者单位

Department of Immunology John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia;

Australian Phenomics Facility, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia;

Department of Biomedical Engineering, Toin University of Yokohama, Aoba-ku, Yokohama 225-8503, Japan;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
IgHm; IgHd; immunoglobulin isotype; ENU mutation;

Zinc-finger protein ZFP318 is essential for expression of IgD, the alternatively spliced Igh product made by mature B lymphocytes

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