B-1a B Cells Regulate T Cell Differentiation Associated with Pregnancy Disturbances

Muzzio, Damián Oscar; Soldati, Rocío; Rolle, L.; Zygmunt, Marek; Zenclussen, Ana Claudia; Jensen, Federico

doi:10.3389/fimmu.2014.00006

Cited by 34 publications

(36 citation statements)

References 31 publications

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“…B cells can also be recruited by the chorioamniotic membranes [14] and constitute a portion of the choriodecidual leukocytes [16,57,58]. The role of B cells during pregnancy and its complications have been widely studied by Jensen and collaborators [59][60][61][62][63][64][65][66][67][68]. Taken together, these data provide further evidence that the adaptive limb of immunity is involved in the process of labor.…”

Section: Resultssupporting

confidence: 52%

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

et al. 2018

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Prior to and during the process of human labor, maternal circulating leukocytes infiltrate the maternal-fetal interface (choriodecidua) and become activated resembling choriodecidual leukocytes. Since, there is no evidence comparing maternal circulating and choriodecidual leukocytes, herein, we characterized their transcriptome and explored the biological processes enriched in choriodecidual leukocytes. From women undergoing spontaneous term labor we isolated circulating and choriodecidual leukocytes, performed microarray analysis (n = 5) and qRT-PCR validation (n = 9) and interaction network analysis with up-regulated genes. We found 270 genes up-regulated and only 17 genes down-regulated in choriodecidual leukocytes compared to maternal circulating leukocytes. The most up-regulated genes were CCL18, GPNMB, SEPP1, FN1, RNASE1, SPP1, C1QC, and PLTP. The biological processes enriched in choriodecidual leukocytes were cell migration and regulation of immune response, chemotaxis, and humoral immune responses. Our results show striking differences between the transcriptome of choriodecidual and maternal circulating leukocytes. Choriodecidual leukocytes are enriched in immune mediators implicated in the spontaneous process of labor at term.

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Section: Resultssupporting

confidence: 52%

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

et al. 2018

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“…Therefore, the suppression of T cell cytokine production by PD-L2 in the context of the germinal center reaction may be unlikely. On the other hand, B-1a cells are known to promote Th1 and Th17 responses, although the ability to polarize Th1/Th17 differentiation has been reported to be independent of PD-L2 (103) since PD-L2 − and PD-L2 + B-1 cells have similar efficacy in eliciting differentiation (104, 105). Nonetheless, our work indicates further investigation into B-1 cell PD-L2–mediated regulation of cytokine production is certainly warranted.…”

Section: Discussionmentioning

confidence: 99%

PD-L2 Regulates B-1 Cell Antibody Production against Phosphorylcholine through an IL-5–Dependent Mechanism

McKay

Haro

Daly

et al. 2017

The Journal of Immunology

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B-1 cells produce natural antibodies which provide an integral first line of defense against pathogens while also performing important homeostatic housekeeping functions. In this study, we demonstrate programmed cell death 1 ligand 2 (PD-L2) regulates the production of natural antibodies against phosphorylcholine (PC). Naïve PD-L2-deficient (PD-L2−/−) mice produced significantly more PC-reactive IgM and IgA. This afforded PD-L2−/− mice with selectively enhanced protection against PC-expressing non-typeable Haemophilus influenzae (NTHi), but not PC-negative NTHi, relative to wild type mice. PD-L2−/− mice had significantly increased PC-specific CD138+ splenic plasmablasts bearing a B-1a phenotype, and produced PC-reactive Abs largely of the T15 idiotype. Importantly, PC-reactive B-1 cells expressed PD-L2 and irradiated chimeras demonstrated B cell-intrinsic PD-L2 expression regulated PC-specific Ab production. In addition to increased PC-specific IgM, naïve PD-L2−/− mice and irradiated chimeras reconstituted with PD-L2−/− B cells had significantly higher levels of IL-5 – a potent stimulator of B-1 cell Ab production. PDL2 mAb blockade of wild type B-1 cells in culture significantly increased CD138 and Blimp1 expression and PC-specific IgM, but did not affect proliferation. PDL2 mAb blockade significantly increased IL-5+ T cells in culture. Both IL-5 neutralization and STAT5 inhibition blunted the effects of PDL2 mAb blockade on B-1 cells. Thus, B-1 cell-intrinsic PD-L2 expression inhibits IL-5 production by T cells and thereby limits natural Ab production by B-1 cells. These findings have broad implications for the development of therapeutic strategies aimed at altering natural Ab levels critical for protection against infectious disease, autoimmunity, allergy, cancer, and atherosclerosis.

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“…27 Research has indicated that downregulation of Th17 cells and maintaining the balance between Th17 and Treg is beneficial to maintaining immune balance of the maternal-fetal interface. 28 Furthermore, we detected the levels of Th1 (IFN-γ), Th2 (IL-10) and Th17 (IL-17) in placental tissue and serum. The secretion of IL-10 mRNA and protein was reduced in decidual tissues of the abortion group, which exhibited increased secretion of IFN-γ mRNA and protein compared with the normal pregnancy control groups.…”

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confidence: 99%

Therapeutic effects of Wharton jelly‐derived mesenchymal stem cells on rat abortion models

Chen

Yang

et al. 2016

J of Obstet and Gynaecol

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Aim: The aim of this study was to investigate the therapeutic effects and mechanism of Wharton jelly-derived mesenchymal stem cells (WJ-MSC) in a spontaneous-abortion rat model. Methods: An abortion model was established using intravenous injection of bromocriptine. WJ-MSC were isolated and cultured from Wharton jelly of the human umbilical cord. The pathologic changes of placenta decidual tissues were observed after hematoxylin-eosin staining. The embryo absorption rate was counted. The protein and mRNA levels of interleukin (IL)-10, interferon (IFN)-γ and IL-17 in each group were tested by enzyme-linked immunosorbent assay, Western blot and quantitative real-time polymerase chain reaction. Results: After bromocriptine injection, decidual cells degenerated and the connections between them loosened. Furthermore, some of the decidual cells were necrotic and the nuclei had disappeared. However, the transplantation of a large population of WJ-MSC prevented these damages from occurring. The changes of levels of IL-10, IFN-γ and IL-17 in serum and placenta decidual tissues induced by bromocriptine were well restored by a high, but not a low, dose of WJ-MSC engraft. Conclusion: WJ-MSC can ameliorate early pregnancy loss. The mechanism may be related to its upregulation of IL-10 and downregulation of IFN-γ and IL-17.

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B-1a B Cells Regulate T Cell Differentiation Associated with Pregnancy Disturbances

Cited by 34 publications

References 31 publications

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

PD-L2 Regulates B-1 Cell Antibody Production against Phosphorylcholine through an IL-5–Dependent Mechanism

Therapeutic effects of Wharton jelly‐derived mesenchymal stem cells on rat abortion models

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