Abstract
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.
Highlights
They can differentiate into mesenchymal tissues such as bone, fat, and cartilage and can be isolated from various tissues, including bone marrow, adipose tissue, and umbilical cord.[1]
We attempted to evaluate the regulatory activity of conditioned medium (CM) of MSCs (MSC-CM) harvested from our clonal MSCs on the Ig production by B cells
When splenic B cells isolated from Balb/c mice were stimulated with lipopolysaccharide (LPS)/ interleukin-4 (IL-4), IgE production was observed (Figure 1a)
Summary
They can differentiate into mesenchymal tissues such as bone, fat, and cartilage and can be isolated from various tissues, including bone marrow, adipose tissue, and umbilical cord.[1] their differentiation potential is not as great as that of embryonic stem cells or induced pluripotent stem cells, MSCs are considered the most promising candidates for clinical applications.[2,3] A characteristic property of MSCs is their immunomodulatory activity.[4] Unlike other pluripotent stem cells, MSCs are not immunogenic when administered in vivo.[5] Instead, they can alleviate host immune responses by suppressing inflammation in instances of inflammatory abnormalities. Mycoplasma arginini produces a lipidassociated membrane lipopeptide that is an agonist of toll-like receptor-2/6.25 This lipopeptide regulates the production of several cytokines via nuclear factor-k B in infected cells.[21]
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