Effect on B Cell Function by Mesenchymal Stem Cells of Different Derivation

Abstract Human mesenchymal stem cells (hMSCs) suppress T-cell and dendritic-cell function and represent a promising strategy for cell therapy of autoimmune diseases. Nevertheless, no information is currently available on the effects of hMSCs on B cells, which may have a large impact on the clinical use of these cells. hMSCs isolated from the bone marrow and B cells purified from the peripheral blood of healthy donors were cocultured with different B-cell tropic stimuli. B-cell proliferation was inhibited by hMSCs through an arrest in the G0/G1 phase of the cell cycle and not through the induction of apoptosis. A major mechanism of B-cell suppression was hMSC production of soluble factors, as indicated by transwell experiments. hMSCs inhibited B-cell differentiation because IgM, IgG, and IgA production was significantly impaired. CXCR4, CXCR5, and CCR7 B-cell expression, as well as chemotaxis to CXCL12, the CXCR4 ligand, and CXCL13, the CXCR5 ligand, were significantly down-regulated by hMSCs, suggesting that these cells affect chemotactic properties of B cells. B-cell costimulatory molecule expression and cytokine production were unaffected by hMSCs. These results further support the potential therapeutic use of hMSCs in immune-mediated disorders, including those in which B cells play a major role.

Download Full-text

Fusokine GIFT4 triggers novel B Cell function on hematopoietic stem cells

Cytotherapy ◽

10.1016/j.jcyt.2015.03.329 ◽

2015 ◽

Vol 17 (6) ◽

pp. S13-S14

Author(s):

Jiusheng Deng ◽

Andrea Pennati ◽

Shala Yuan ◽

Edmund Waller ◽

Sagar Lonial ◽

...

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

B Cell ◽

Cell Function ◽

Hematopoietic Stem ◽

B Cell Function

Download Full-text

HIV-mediated Expression of Btk in Hematopoietic Stem Cells is not Sufficient to Restore B Cell Function in X-linked Immunodeficient Mice

Journal of Nippon Medical School ◽

10.1272/jnms.72.203 ◽

2005 ◽

Vol 72 (4) ◽

pp. 203-212 ◽

Cited By ~ 2

Author(s):

Hiroko Tanabe ◽

Koichi Miyake ◽

Takashi Shimada

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

B Cell ◽

Cell Function ◽

Hematopoietic Stem ◽

Immunodeficient Mice ◽

B Cell Function

Download Full-text

EBF1 is expressed in pericytes and contributes to pericyte cell commitment

Histochemistry and Cell Biology ◽

10.1007/s00418-021-02015-7 ◽

2021 ◽

Author(s):

Francesca Pagani ◽

Elisa Tratta ◽

Patrizia Dell’Era ◽

Manuela Cominelli ◽

Pietro Luigi Poliani

Keyword(s):

Stem Cells ◽

Endothelial Cells ◽

Mesenchymal Stem Cells ◽

B Cell ◽

Cell Fate ◽

Early Stage ◽

Cell Lineage ◽

Cell Maturation ◽

Cell Commitment

AbstractEarly B-cell factor-1 (EBF1) is a transcription factor with an important role in cell lineage specification and commitment during the early stage of cell maturation. Originally described during B-cell maturation, EBF1 was subsequently identified as a crucial molecule for proper cell fate commitment of mesenchymal stem cells into adipocytes, osteoblasts and muscle cells. In vessels, EBF1 expression and function have never been documented. Our data indicate that EBF1 is highly expressed in peri-endothelial cells in both tumor vessels and in physiological conditions. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and fluorescence-activated cell sorting (FACS) analysis suggest that EBF1-expressing peri-endothelial cells represent bona fide pericytes and selectively express well-recognized markers employed in the identification of the pericyte phenotype (SMA, PDGFRβ, CD146, NG2). This observation was also confirmed in vitro in human placenta-derived pericytes and in human brain vascular pericytes (HBVP). Of note, in accord with the key role of EBF1 in the cell lineage commitment of mesenchymal stem cells, EBF1-silenced HBVP cells showed a significant reduction in PDGFRβ and CD146, but not CD90, a marker mostly associated with a prominent mesenchymal phenotype. Moreover, the expression levels of VEGF, angiopoietin-1, NG2 and TGF-β, cytokines produced by pericytes during angiogenesis and linked to their differentiation and activation, were also significantly reduced. Overall, the data suggest a functional role of EBF1 in the cell fate commitment toward the pericyte phenotype.

Download Full-text

B cell-specific GPR55 deficiency promotes atherosclerosis

European Heart Journal ◽

10.1093/ehjci/ehaa946.3785 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

R Guillamat-Prats ◽

D Hering ◽

M Rami ◽

C Haerdtner ◽

L Bindila ◽

...

Keyword(s):

Body Weight ◽

B Cells ◽

B Cell ◽

Mrna Expression ◽

Cell Function ◽

Metabolic Effects ◽

Atherosclerotic Plaques ◽

Funding Source ◽

Sequencing Analysis ◽

B Cell Function

Abstract Background Atherosclerosis is accompanied by an imbalance between resolving and pro-inflammatory lipid mediators. Targeting lipid signaling pathways might offer a new anti-inflammatory therapy for improving the clinical outcome in cardiovascular disease patients. We considered lysophosphatidylinositol (LPI) and its receptor G protein-coupled receptor (GPR)55 as a potential modulator of atherosclerosis. Its role in regulating atherosclerosis and B cell function is unknown. Hypothesis We assessed the hypothesis that GPR55 signaling causally affects atherosclerosis and whether it has a specific role in regulating B cell function in this disease. Methods Atherosclerotic plaques were compared between apolipoprotein E deficient (ApoE−/−) and ApoE−/−Gpr55−/− mice after 4 to 16 weeks Western Diet (WD; 0.15% cholesterol; n=12–15 per group). To specifically test the role of B cell GPR55 in atherosclerosis, we generated mixed chimeras by lethally irradiating low density lipoprotein receptor deficient (Ldlr−/−) mice and reconstituting with a mixture of μMT and wildtype (control) or μMT and Gpr55−/− bone marrow cells. Circulating B cells were sorted and bulk RNA sequencing analysis was performed. We performed lipid and immunostainings of murine aortic root plaques, qPCR and ELISA of tissue lysates, as well as multiplex analysis of plasma immunoglobulins. Leukocyte plasma and tissue counts were determined by flow cytometry. Results GPR55 expression in mouse and human atherosclerotic plaques was detected by immunostaining. Furthermore, we confirmed murine Gpr55 mRNA expression on sorted circulating B220+B cells via qPCR, which was higher compared to CD3+ T cells, while CD11+ myeloid cells as well as NK cells had only low Gpr55 mRNA levels. ApoE−/−Gpr55−/− mice had significantly larger plaques after 4&16 weeks WD compared to ApoE−/− controls, with more pronounced body weight increases and higher cholesterol levels at the 16 weeks WD time point. In addition, global Gpr55 deficiency resulted in enhanced aortic pro-inflammatory cytokine mRNA expression (IL-1β, IL-6, TNFα) and a massively upregulated IgG1 plasma levels and increased percentages of splenic germinal center and plasma cells. B-cell RNA-seq analysis showed 460 differential expressed regulated genes in the ApoE−/−Gpr55−/− compared to ApoE−/−. The main pathways affected were calcium ion transport, immunoglobulin production, negative regulation of phosphorylation, and cellular component morphogenesis, suggesting a dsysregulation of B cell function. B cell specific Gpr55 deficiency blunted the metabolic effects on body weight and cholesterol, but still translated in larger atherosclerotic plaques and elevated plasma IgG levels compared to the respective controls. Conclusion Both global and B cell-restricted Gpr55 deficiency promotes atherosclerosis and is associated with a more pro-inflammatory phenotype. Our findings suggest a novel role for GPR55 in regulating B cell development and function. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft (DFG)

Download Full-text