Immunoglobulin G Expression in Human Sperm and Possible Functional Significance

Yan, Meiling; Zhang, Xiaoyu; Pu, Qinxue; Huang, Tao; Xie, Qiang; Wang, Yan; Li, Jing; Wang, Yun; Gu, Huan; Huang, Tian-Hua; Li, Zhiling; Gu, Jiang

doi:10.1038/srep20166

Cited by 13 publications

(16 citation statements)

References 34 publications

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“…Antibodies, also known as immunoglobulins (Igs), are expressed by B lymphocytes; however, accumulating evidence has indicated that Igs, including IgG, IgA and IgM, are produced in non-B lineage cells, such as epithelial cancer cells ( 6 – 9 ) and leukemic cells ( 10 – 12 ). Furthermore, several types of normal cells, including germ cells ( 13 , 14 ), neurons ( 15 , 16 ), endothelial cells ( 17 ) and skin epidermal cells ( 18 ), can also express Igs. Although non-B cell-derived Ig and traditional Ig have some similar characteristics, the former possesses unique characteristics, particularly with regards to structure and function.…”

Section: Introductionmentioning

confidence: 99%

Expression of immunoglobulin G in human podocytes, and its role in cell viability and adhesion

Jing

Deng

et al. 2018

Int J Mol Med

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Podocyte injury occurs during the initiation and development of numerous forms of glomerular disease, and antibodies targeting podocytes have become a biomarker for diagnosis and monitoring treatment response. Accumulating evidence has suggested that immunoglobulin (Ig) is expressed in non-B lineage cells, including epithelial cancer cells, myeloid cells and several types of normal cells. The main aim of the present study was to ascertain the expression of IgG in human podocytes and to determine its potential role in cellular bioactivity. The present study detected positive staining for IgG heavy chain (Igγ) and its subtype γ4, and the light chains κ and λ in the cytoplasm or on the membrane by immunofluorescence. In addition, positive bands were detected for Igγ, γ1, γ3, γ4, κ and λ in the lysates of a podocyte cell line by western blotting. Mass spectrometry confirmed IgG1 as an intact tetramer in the culture supernatant. Constant region transcripts of Igγ, γ1, γ3, γ4, κ and λ were identified by reverse transcription-polymerase chain reaction, and DNA sequencing of these transcripts revealed 96–99% similarity with Ig mRNAs in the National Center for Biotechnology Information database. Compared with the diverse gene rearrangements from B cell-derived Ig, podocyte-derived Ig exhibited conservative V(D)J patterns in the variable regions of Igγ and κ chains. Furthermore, the present study investigated the mechanism underlying IgG production in these cells by examining the expression of recombination activating gene (RAG)1, RAG2 and activation-induced cytidine deaminase. The expression levels of these proteins suggested that podocyte-derived Ig and traditional Ig may be generated in a similar manner. Furthermore, small interfering RNA-mediated downregulation of IgG expression reduced podocyte viability and adhesive capabilities. These findings suggested that IgG is expressed in podocytes and that this expression may be associated with podocyte function. Due to its potential biological and clinical significance, this phenomenon warrants further investigation.

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Section: Introductionmentioning

confidence: 99%

Expression of immunoglobulin G in human podocytes, and its role in cell viability and adhesion

Jing

Deng

et al. 2018

Int J Mol Med

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“…Antibodies are normally synthesized by mature plasma cells. However, recent accumulating evidence suggests that non-lymphoid cells, such as human sperm ( 31 ), hepatocytes ( 32 ), certain carcinoma cells ( 25 , 32 , 33 ), and neurons from the central nervous system ( 34 – 37 ), also express genes required for antibody synthesis and produce antibodies. Here, we demonstrate that although DRG sensory neurons exhibit localization of antigen-specific antibodies, the neuronal cells do not express the essential enzymes required for generating antibody diversity.…”

Section: Discussionmentioning

confidence: 99%

Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons

et al. 2018

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The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs) of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR), dorsal root ganglion (DRG) sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG) required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO) or μMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM) into wild-type (WT) mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses.

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“…IgG and RAG-1/RAG-2 expression was recently detected in human sperm, and an anti-IgG antibody was shown to inhibit sperm penetration of Zona-free hamster egg (Yan et al, 2016). Thus, sumoylation of RAG-1, which, to the best of our knowledge, has not previously reported, may be of importance in fertilization.…”

Section: Discussionmentioning

confidence: 99%

“…Beyond cytoskeleton regulation, RAG1, which is essential for IgG immunoglobulin synthesis and class switching, was another potentially important SUMO1 targets identified in this study. IgG and RAG-1/RAG-2 expression was recently detected in human sperm, and an anti-IgG antibody was shown to inhibit sperm penetration of Zona-free hamster egg (Yan et al, 2016 ). Thus, sumoylation of RAG-1, which, to the best of our knowledge, has not previously reported, may be of importance in fertilization.…”

Section: Discussionmentioning

confidence: 99%

Expression, Localization of SUMO-1, and Analyses of Potential SUMOylated Proteins in Bubalus bubalis Spermatozoa

et al. 2017

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Mature spermatozoa have highly condensed DNA that is essentially silent both transcriptionally and translationally. Therefore, post translational modifications are very important for regulating sperm motility, morphology, and for male fertility in general. Protein sumoylation was recently demonstrated in human and rodent spermatozoa, with potential consequences for sperm motility and DNA integrity. We examined the expression and localization of small ubiquitin-related modifier-1 (SUMO-1) in the sperm of water buffalo (Bubalus bubalis) using immunofluorescence analysis. We confirmed the expression of SUMO-1 in the acrosome. We further found that SUMO-1 was lost if the acrosome reaction was induced by calcium ionophore A23187. Proteins modified or conjugated by SUMO-1 in water buffalo sperm were pulled down and analyzed by mass spectrometry. Sixty proteins were identified, including proteins important for sperm morphology and motility, such as relaxin receptors and cytoskeletal proteins, including tubulin chains, actins, and dyneins. Forty-six proteins were predicted as potential sumoylation targets. The expression of SUMO-1 in the acrosome region of water buffalo sperm and the identification of potentially SUMOylated proteins important for sperm function implicates sumoylation as a crucial PTM related to sperm function.

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Immunoglobulin G Expression in Human Sperm and Possible Functional Significance

Cited by 13 publications

References 34 publications

Expression of immunoglobulin G in human podocytes, and its role in cell viability and adhesion

Expression of immunoglobulin G in human podocytes, and its role in cell viability and adhesion

Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons

Expression, Localization of SUMO-1, and Analyses of Potential SUMOylated Proteins in Bubalus bubalis Spermatozoa

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