Identification of Liver Epithelial Cell-derived Ig Expression in μ chain-deficient mice

Shao, Wenwei; Zhang, Chi; Liu, Enyang; Zhang, Long; Ma, Jiamin; Zhu, Zhu; Gong, Xiaoting; Qin, Zhihai; Qiu, Xiaoyan

doi:10.1038/srep23669

Cited by 23 publications

(17 citation statements)

References 40 publications

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“…Positive staining of Igγ, γ4, κ and λ chains was detected in the cytoplasm of podocytes, thus indicating that podocytes may express IgG. Shao et al ( 35 ) reported that IgM was expressed and presented in kidney tubules in µ MT mice, which have hardly any IgM in circulation due to the disruption of the µ heavy chain, thus lacking mature B cells. Compared with commercial antibodies, the RP215 antibody recognizes a specific carbohydrate-associated epitope on non-B cell-derived Igγ ( 34 ); in the present study, RP215 mAb detected IgG more clearly both on the cell membranes and in the cytoplasm, suggesting that podocyte-derived IgG was more likely to be non-B cell derived as the findings of Liao et al ( 26 ).…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…In this context, Ig synthesis has largely been considered an aberrant feature of transformed somatic cells. However, recent studies in neuronal cells [ 46 ], epithelial cells [ 47 ], epidermal cells [ 48 ] and endothelial cells [ 49 ] suggest that non-transformed cell types are also capable of “ectopic” immunoglobulin production.…”

Section: Discussionmentioning

confidence: 99%

Expression of combinatorial immunoglobulins in macrophages in the tumor microenvironment

et al. 2018

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Recent evidence indicates the presence of macrophage subpopulations that express the TCRαβ in chronic inflammatory diseases such as tuberculosis and atherosclerosis and in the tumor microenvironment. Here, we demonstrate that a second subpopulation of macrophages expresses rearranged heavy and light chain immunoglobulins. We identify immunoglobulin expression in human and murine monocytes, in ex vivo differentiated macrophages and macrophages from the tumor microenvironment of five randomly selected distinct human tumor entities. The immunoglobulin heavy and light chains are expressed in a small macrophage subfraction (~3–5%) as combinatorial and individual-specific immune receptors. Using Sanger sequencing and deep sequencing, we routinely find markedly restricted Ig repertoires in monocytes/macrophages compared to normal B cells. Furthermore, we report the complete Ig heavy and light chain sequences of a fully functional immunoglobulin from a single tumor-associated macrophage. These results demonstrate that Ig expression is a defining feature of monocytes and also macrophages in the tumor microenvironment and thus reveal an as yet unrecognized modus operandi of host defense in professional phagocytes.

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“…Our single cell sequencing results showed that, unlike B cell-derived Igk, which shows diversity, cardiomyocyte-derived Igk exhibited a very conservative VkJk usage and pattern and tended to express IgkV17-121 (28.3%, 95/336), IgkV9-120 (25%, 84/336), and IgkV14-100 (15.5%, 52/336) in cardiomyocytes in adult mice. It is worth noting that the conservative characteristics of cardiomyocyte-derived Igk were similar to those of Igk in hepatocytes and other non-B cells, especially IgkV9-120, which has been found to be highly frequently expressed in other non-B cell lineages 34,35 . However, the expression frequency of the above VkJk usages in B cells was less than 3%.…”

Section: Discussionmentioning

confidence: 73%

“…For several decades, B cells and differentiated plasma cells were thought to be the only sources of Igs. However, in recent years, many studies from our group and others have revealed that Igs are not only produced by B cells but also expressed by non-B cell lineages, including epithelial cells, neurons and germ cells of the testis [1][2][3][4][5][6][7][8] . In addition to serving as natural antibodies for immune defense, non-B Igs also exhibit diverse biological functions; for example, renal podocyte-derived IgG promotes cell adhesion and survival 9,10 .…”

Section: Introductionmentioning

confidence: 99%

Immunoglobulin kappa light chain produced by cardiomyocytes and participates in maintaining intercalated disc integrity

Qiu¹,

Zhu²,

Shi³

et al. 2020

Preprint

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It is widely accepted that immunoglobulins (Igs) are produced only by B cells and function as antibodies. However, growing evidence has proven that almost all non-B cells also produce Igs with nonconventional roles, such as promotion of cell survival, proliferation and migration. In this study, we identified Ig light chain (κ chain) expression in mouse and human cardiomyocytes, especially on intercalated discs (ICDs). Unexpectedly, conditional knockout (cKO) of Igκ in adult cardiomyocytes in mice resulted in significant hypotension, a rapid decrease in cardiac contractility and conduction defects. Histologically, Igκ knockout in mouse cardiomyocytes led to structural disruption of intercalated discs (ICDs) and loss of localization of adhesion-related N-cadherin and CX43 on ICDs. Mechanistic investigation indicated that Igκ can bind with plectin/desmoplakin, a complex that connects desmin and desmosomes and enhances the protein stability of plectin. In conclusion, Our findings identify Igκ expressed by cardiomyocytes as a new ICD-related molecule that participates in cardiomyocyte contraction and conduction by stabilizing plectin.

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Identification of Liver Epithelial Cell-derived Ig Expression in μ chain-deficient mice

Cited by 23 publications

References 40 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

Expression of combinatorial immunoglobulins in macrophages in the tumor microenvironment

Immunoglobulin kappa light chain produced by cardiomyocytes and participates in maintaining intercalated disc integrity

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