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Interaction of Serum-Derived and Internalized C3 With DNA in Human B Cells-A Potential Involvement in Regulation of Gene Transcription

Kremlitzka, Mariann LU ; Nowacka, Alicja A. LU ; Mohlin, Frida C. LU ; Bompada, Pradeep LU ; De Marinis, Yang LU and Blom, Anna M. LU orcid (2019) In Frontiers in Immunology 10.
Abstract

Beside its classical role as a serum effector system of innate immunity, evidence is accumulating that complement has an intracellular repertoire of components that provides not only immune defense, but also functions to maintain cellular homeostasis. While complement proteins, mainly the central component C3, have been detected in B cells, their exact function and source remain largely unexplored. In this study, we investigated the expression and origin of intracellular C3 in human B cells together with its role in B cell homeostasis. Our data provide evidence that endogenous expression of C3 is very low in human B cells and, in accordance with the recent publication, the main origin of intracellular C3 is the serum. Interestingly, we... (More)

Beside its classical role as a serum effector system of innate immunity, evidence is accumulating that complement has an intracellular repertoire of components that provides not only immune defense, but also functions to maintain cellular homeostasis. While complement proteins, mainly the central component C3, have been detected in B cells, their exact function and source remain largely unexplored. In this study, we investigated the expression and origin of intracellular C3 in human B cells together with its role in B cell homeostasis. Our data provide evidence that endogenous expression of C3 is very low in human B cells and, in accordance with the recent publication, the main origin of intracellular C3 is the serum. Interestingly, we found that both serum-derived and purified C3 are able to enter the nucleus of viable B cells, suggesting its potential involvement in regulation of gene transcription. ELISA, gel shift assay, confocal microscopy, and chromatin immunoprecipitation proved that C3 and C3a strongly bind to nuclear DNA, and among the interacting genes there are key factors of lymphocyte development and differentiation. The strong interaction of C3 with histone proteins and its potential ability to induce chromatin rearrangement suggest that C3/C3a might regulate DNA transcription via chromatin remodeling. Our data reveal a novel, hitherto undescribed role of C3 in immune cell homeostasis, which further extends the repertoire how complement links innate and adaptive immunity and regulates basic processes of the cells.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
complement C3, DNA, gene transcription, histones, internalization
in
Frontiers in Immunology
volume
10
article number
493
publisher
Frontiers Media S. A.
external identifiers
  • pmid:30941132
  • scopus:85064230388
ISSN
1664-3224
DOI
10.3389/fimmu.2019.00493
language
English
LU publication?
yes
id
3f394c8c-1536-426f-8d24-504c32b18353
date added to LUP
2019-05-02 12:08:07
date last changed
2024-12-26 06:35:44
@article{3f394c8c-1536-426f-8d24-504c32b18353,
  abstract     = {{<p>Beside its classical role as a serum effector system of innate immunity, evidence is accumulating that complement has an intracellular repertoire of components that provides not only immune defense, but also functions to maintain cellular homeostasis. While complement proteins, mainly the central component C3, have been detected in B cells, their exact function and source remain largely unexplored. In this study, we investigated the expression and origin of intracellular C3 in human B cells together with its role in B cell homeostasis. Our data provide evidence that endogenous expression of C3 is very low in human B cells and, in accordance with the recent publication, the main origin of intracellular C3 is the serum. Interestingly, we found that both serum-derived and purified C3 are able to enter the nucleus of viable B cells, suggesting its potential involvement in regulation of gene transcription. ELISA, gel shift assay, confocal microscopy, and chromatin immunoprecipitation proved that C3 and C3a strongly bind to nuclear DNA, and among the interacting genes there are key factors of lymphocyte development and differentiation. The strong interaction of C3 with histone proteins and its potential ability to induce chromatin rearrangement suggest that C3/C3a might regulate DNA transcription via chromatin remodeling. Our data reveal a novel, hitherto undescribed role of C3 in immune cell homeostasis, which further extends the repertoire how complement links innate and adaptive immunity and regulates basic processes of the cells.</p>}},
  author       = {{Kremlitzka, Mariann and Nowacka, Alicja A. and Mohlin, Frida C. and Bompada, Pradeep and De Marinis, Yang and Blom, Anna M.}},
  issn         = {{1664-3224}},
  keywords     = {{complement C3; DNA; gene transcription; histones; internalization}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Interaction of Serum-Derived and Internalized C3 With DNA in Human B Cells-A Potential Involvement in Regulation of Gene Transcription}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2019.00493}},
  doi          = {{10.3389/fimmu.2019.00493}},
  volume       = {{10}},
  year         = {{2019}},
}