First Author | Pioli PD | Year | 2014 |
Journal | J Immunol | Volume | 193 |
Issue | 5 | Pages | 2546-53 |
PubMed ID | 25057009 | Mgi Jnum | J:215815 |
Mgi Id | MGI:5606278 | Doi | 10.4049/jimmunol.1401275 |
Citation | Pioli PD, et al. (2014) Zfp318 regulates IgD expression by abrogating transcription termination within the Ighm/Ighd locus. J Immunol 193(5):2546-53 |
abstractText | The protein Zfp318 is expressed during the transition of naive B cells from an immature to mature state. To evaluate its role in mature B cell functions, a conditional gene deficiency in Zfp318 was created and deleted in bone marrow lineages via Vav-Cre. B cell development was minimally altered in the absence of the protein, although transitional 2 (T2) B cell populations were depressed in the absence of Zfp318. Intriguingly, the analysis of IgM and IgD expression by maturing and mature naive B cells demonstrated an elevated level of IgM gene products and a virtual loss of IgD products. Transcriptome analysis of Zfp318-deficient B cells revealed that only two gene products showed altered expression in the absence of Zfp318 (Ighd and Sva), demonstrating a remarkable specificity of Zfp318 action. In the absence of Zfp318, Ighm/Ighd transcripts, which would normally encode IgM and IgD from heterogeneous nuclear RNA transcripts via alternative splicing, lack intron and exon sequences from the IgD (Ighd)-encoding region. This finding indicates that Zfp318, in a novel manner, functions by repressing recognition of the transcriptional termination site at the 3' end of the terminal IgM-encoding exon, allowing for synthesis of the complete Ighm/Ighd heterogeneous nuclear RNA. |