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Depletion of conventional mature B cells and compromised specific antibody response in bovine immunoglobulin μ heavy-chain transgenic mice

Min ZHANG,Xueqian CHENG,Dan CHU,Jingwen LIANG,Yi SUN,Li MA,Beilei XU,Min ZHENG,Meili WANG,Liming REN,Xiaoxiang HU,Qingyong MENG,Ran ZHANG,Ying GUO,Yunping DAI,Robert AITKEN,Ning LI,Yaofeng ZHAO

《农业科学与工程前沿（英文）》 2014年 第1卷 第2期   页码 158-173 doi: 10.15302/J-FASE-2014015

摘要： In this study, we introduced the bovine immunoglobulin μ heavy-chain gene (the orphaned gene on BTA11) into mouse germline cells. Bovine IgM was highly expressed in selected transgenic lines, and it largely inhibited rearrangements of the endogenous immunoglobulin heavy chain (IgH) genes in these lines. The forced expression of bovine IgM resulted in reduced numbers of pro- and pre-B cells but increased the number of immature B cells in the transgenic mice. Bovine IgM-expressing B cells can migrate from the bone marrow to the spleen, but most of the cells are arrested at the T1 transitional B cell stage, leading to a significantly lower number of T2 transitional and mature B cells in the spleen. Although the serum concentrations of endogenous IgM and IgG in the transgenic mice were significantly decreased, the IgA levels were slightly increased compared to the WT mice. The bovine IgM level in the serum was only one-tenth to one-fifth of that of endogenous mouse IgM, suggesting that most of the serum immunoglobulin were contributed by endogenous IgH gene-expressing B cells. These transgenic mice also exhibited a lower frequency of unique complementarity determining region 3 (CDR3) sequences in their VH repertoire and Vκ repertoire but exhibited an increased frequency of unique CDR3 in their Vλ repertoire. Compared to the WT mice, the transgenic mice had a significantly higher percentage of mouse IgM-expressing B cells that expressed λ chains. Finally, we showed that the transgenic mice were deficient in a specific antibody response to antigen stimulation.

关键词： bovine Ig μ heavy-chain     transgenic mice     B cell development     allelic exclusion     immune response     Ig repertoire    

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Development of the expressed immunoglobulin μ chain repertoire during maturation of mice B cells

Jingwen LIANG,Yingfeng LUO,Yi SUN,Meng LEI,Bing ZHANG,Songnian HU,Yaofeng ZHAO

《农业科学与工程前沿（英文）》 2014年 第1卷 第3期   页码 201-213 doi: 10.15302/J-FASE-2014017

摘要： In the bone marrow and spleen, the developing B cell populations undergo both negative and positive selections to shape their B cell receptor repertoire. To gain insight into the shift of the immunoglobulin heavy (IgH) chain repertoire during B cell development, we undertook large scale Ig μ chain repertoire analysis of pre-B, immature B and spleen B cell populations. We found that the majority of V gene segments, V families, J and D gene segments, were observed to have significantly different usage frequencies when three B cell populations were compared, but the usage profile of the V D, and J genes between different B cell populations showed high correlations. In both productive and nonproductive rearrangements, the length of CDRH3 shortened significantly on average when B cells entered the periphery. However, the CDRH3 length distribution of nonproductive rearrangements did not follow a Gaussian distribution, but decreased successively in the order 3 -2, 3 -1 and 3 , suggesting a direct correlation between mRNA stability and CDRH3 length patterns of nonproductive rearrangements. Further analysis of the individual components comprising CDRH3 of productive rearrangements indicated that the decrease in CDRH3 length was largely due to the reduction of N addition at the 5′ and 3′ junctions. Moreover, with development, the amino acid content of CDRH3 progressed toward fewer positively charged and nonpolar residues but more polar residues. All these data indicated that the expressed Ig μ chain repertoire, especially the repertoire of CDRH3, was fine-tuned when B cells passed through several checkpoints of selection during the process of maturation.

关键词： repertoire     complementarity determining region 3 of the IgH chain (CDRH3)     immunoglobulin     heavy chain     variable region    

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Structural prediction of porcine sialoadhesin V-set Ig-like domain sheds some light on its role in porcine

Jie HOU,Rui LI,Hongfang MA,Songlin QIAO,Gaiping ZHANG

《农业科学与工程前沿（英文）》 2016年 第3卷 第1期   页码 65-71 doi: 10.15302/J-FASE-2016086

摘要： Porcine reproductive and respiratory syndrome (PRRS) is characterized by reproductive failures in sows and respiratory diseases in pigs of all ages. PRRS virus (PRRSV) is its causative agent and has caused huge economic losses in the swine industry. Porcine sialoadhesin (pSn) is a putative receptor of PRRSV. Previous studies have shown that a pSn V-set Ig-like domain is significant in PRRSV infection. However, its structural details are not fully known, hindering our deep understanding of PRRSV infection. In this study, we successfully cloned, expressed and purified the pSn V-set Ig-like domain in S2 cells. Then we tried to crystallize the target protein and predicted its structure. This will establish the foundation for the further structural study of pSn, deepen our understanding of the invasion mechanism of PRRSV, and support the structural information for the development of clinical drugs and vaccines against PRRSV.

关键词： PRRSV     porcine sialoadhesin     V-set Ig-like domain     Drosophila S2 cell     crystallization    

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Erratum to “Targeted Genotyping of a Whole-Gene Repertoire by an Ultrahigh-Multiplex and Flexible HD-Marker Erratum

Pingping Liu,Jia Lv,Cen Ma,Tianqi Zhang,Xiaowen Huang,Zhihui Yang,Lingling Zhang,Jingjie Hu,Shi Wang,Zhenmin Bao,

《工程（英文）》 2022年 第18卷 第11期   页码 259-259 doi: 10.1016/j.eng.2022.09.002

关键词： online     THE AUTHORS.Published     repertoire     behalf     Engineering     September     genotyping     Academy     HD-marker approach”     Education Press Limited Company.    

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标题 作者 时间 类型 操作

Depletion of conventional mature B cells and compromised specific antibody response in bovine immunoglobulin μ heavy-chain transgenic mice

Min ZHANG,Xueqian CHENG,Dan CHU,Jingwen LIANG,Yi SUN,Li MA,Beilei XU,Min ZHENG,Meili WANG,Liming REN,Xiaoxiang HU,Qingyong MENG,Ran ZHANG,Ying GUO,Yunping DAI,Robert AITKEN,Ning LI,Yaofeng ZHAO

期刊论文

Development of the expressed immunoglobulin μ chain repertoire during maturation of mice B cells

Jingwen LIANG,Yingfeng LUO,Yi SUN,Meng LEI,Bing ZHANG,Songnian HU,Yaofeng ZHAO

期刊论文

Structural prediction of porcine sialoadhesin V-set Ig-like domain sheds some light on its role in porcine

Jie HOU,Rui LI,Hongfang MA,Songlin QIAO,Gaiping ZHANG

期刊论文

Erratum to “Targeted Genotyping of a Whole-Gene Repertoire by an Ultrahigh-Multiplex and Flexible HD-Marker

Pingping Liu,Jia Lv,Cen Ma,Tianqi Zhang,Xiaowen Huang,Zhihui Yang,Lingling Zhang,Jingjie Hu,Shi Wang,Zhenmin Bao,

期刊论文