Mesenchymal stem cells infected with Mycoplasma arginini secrete complement C3 to regulate immunoglobulin production in B lymphocytes.
Mesenchymal stem cells (MSCs) have immunomodulatory functions such as the suppression of T and B cells. MSCs suppress immunoglobulin (Ig) production by B cells via cell-cell contact as well as via secretion of soluble factors. Our study showed that the conditioned medium (CM) of MSCs infected with a mycoplasma strain, Mycoplasma arginini, has marked inhibitory effects on Ig production by lipopolysaccharide/interleukin-4-induced B cells compared with mycoplasma-free MSC-CM. We analyzed mycoplasma-infected MSC-CM by fast protein liquid chromatography and liquid chromatography to screen the molecules responsible for Ig inhibition. Complement C3 (C3) was the most critical molecule among the candidates identified. C3 was shown to be involved in the suppression of the Ig production of B cells. C3 was secreted by mycoplasma-infected MSCs, but not by mycoplasma-free MSCs or B cells. It was able to directly inhibit Ig production by B cells. In the presence of a C3 inhibitor, Ig inhibition by MSC-CM was abrogated. This inhibitory effect was concomitant with the downregulation of B-cell-induced maturation protein-1, which is a regulator of the differentiation of antibody-secreting plasma cells. These results suggest that C3 secreted from mycoplasma-infected MSCs has an important role in the immunomodulatory functions of MSCs. However, its role in vivo needs to be explored.
Department of Biomedical Sciences, Inha University School of Medicine, Incheon, Republic of Korea.
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Lee
1] Translational Research Center, Inha University School of Medicine, Incheon, Republic of Korea [2] Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon, Republic of Korea.
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Yi
Drug Development Program, Department of Medicine, Inha University School of Medicine, Incheon, Republic of Korea.
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Lee
Drug Development Program, Department of Medicine, Inha University School of Medicine, Incheon, Republic of Korea.
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Kim
College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul, Republic of Korea.
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Park
Translational Research Center, Inha University School of Medicine, Incheon, Republic of Korea.
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Jeon
1] Department of Biomedical Sciences, Inha University School of Medicine, Incheon, Republic of Korea [2] Translational Research Center, Inha University School of Medicine, Incheon, Republic of Korea.
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Song
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D007073:Immunoglobulin E / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D008070:Lipopolysaccharides; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000382:microbiology*; D051379:Mice; D009174:Mycoplasma / Q000187:drug effects / Q000276:immunology*
D003176:Complement C3; D017077:Culture Media, Conditioned; D007136:Immunoglobulins; D008070:Lipopolysaccharides; C036757:lipopolysaccharide B; D007073:Immunoglobulin E