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

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          Abstract

          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 H gene segments, V H families, J H 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 H, D, and J H 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 n-2, 3 n-1 and 3 n, 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.

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          Most cited references 57

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          Predominant autoantibody production by early human B cell precursors.

          During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage of this process is that some of the antibodies produced are self-reactive. We determined the prevalence of self-reactive antibody formation and its regulation in human B cells. A majority (55 to 75%) of all antibodies expressed by early immature B cells displayed self-reactivity, including polyreactive and anti-nuclear specificities. Most of these autoantibodies were removed from the population at two discrete checkpoints during B cell development. Inefficient checkpoint regulation would lead to substantial increases in circulating autoantibodies.
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            A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance.

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              Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice.

              Immunological tolerance has been demonstrated in double-transgenic mice expressing the genes for a neo-self antigen, hen egg lysozyme, and a high affinity anti-lysozyme antibody. The majority of anti-lysozyme B-cells did not undergo clonal deletion, but were no longer able to secrete anti-lysozyme antibody and displayed markedly reduced levels of surface IgM while continuing to express high levels of surface IgD. These findings indicate that self tolerance may result from mechanisms other than clonal deletion, and are consistent with the hypothesis that IgD may have a unique role in B-cell tolerance.
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                Author and article information

                Journal
                Front. Agr. Sci. Eng.
                FASE
                CN10-1204/S
                Frontiers of Agricultural Science and Engineering
                Higher Education Press (4 Huixin Dongjie, Chaoyang District, Beijing 100029, China )
                2095-7505
                2014
                : 1
                : 3
                : 201-213
                Affiliations
                1. State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100094, China
                2. CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
                3. Laboratory of Animal Molecular Genetics, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Taian 271018, China
                Author notes
                husn@big.ac.cn
                yaofengzhao@cau.edu.cn
                Article
                10.15302/J-FASE-2014017

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Categories
                RESEARCH ARTICLE

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