Zfp318 Regulates IgD Expression by Abrogating Transcription Termination within the Ighm/Ighd Locus
JOURNAL OF IMMUNOLOGY
Authors: Pioli, Peter D.; Debnath, Irina; Weis, Janis J.; Weis, John H.
Abstract
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.
Revisiting the Pig IGHC Gene Locus in Different Breeds Uncovers Nine Distinct IGHG Genes
JOURNAL OF IMMUNOLOGY
Authors: Zhang, Ming; Li, Zhenrong; Li, Jingying; Huang, Tian; Peng, Gaochuang; Tang, Wenda; Yi, Guoqiang; Zhang, Lifan; Song, Yu; Liu, Tianran; Hu, Xiaoxiang; Ren, Liming; Liu, Honglin; Butler, John E.; Han, Haitang; Zhao, Yaofeng
Abstract
IgG subclass diversification is common in placental mammals. It has been well documented in humans and mice that different IgG subclasses, with diversified functions, synergistically regulate humoral immunity. However, our knowledge on the genomic and functional diversification of IgG subclasses in the pig, a mammalian species with high agricultural and biomedical importance, is incomplete. Using bacterial artificial chromosome sequencing and newly assembled genomes generated by the PacBio sequencing approach, we characterized and mapped the IgH C region gene locus in three indigenous Chinese breeds (Erhualian, Xiang, and Luchuan) and compared them to that of Duroc. Our data revealed that IGHG genes in Chinese pigs differ from the Duroc, whereas the IGHM, IGHD, IGHA, and IGHE genes were all single copy and highly conserved in the pig breeds examined. Most striking were differences in numbers of IGHG genes: there are seven genes in Erhualian pigs, six in the Duroc, but only five in Xiang pigs. Phylogenetic analysis suggested that all reported porcine IGHG genes could be classified into nine subclasses: IGHG1, IGHG2a, IGHG2b, IGHG2c, IGHG3, IGHG4, IGHG5a, IGHG5b, and IGHG5c. Using sequence information, we developed a mouse mAb specific for IgG3. This study offers a starting point to investigate the structure-function relationship of IgG subclasses in pigs.