Session Information
Title: B cell Biology and Targets in Autoimmune Disease: Systemic Lupus Erythematosus and Related Diseases
Session Type: Abstract Submissions (ACR)
Background/Purpose: Human mesenchymal stem cells (MSC) are progenitor cells that have immunomodulatory properties. MSCs have been used to treat a variety of autoimmune diseases, including lupus. However, literatures have reported conflicting results of MSC function in regards to B cell biological behaviors. We tested the ability of MSCs from umbilical cords, and MSCs from healthy and lupus bone marrow in modulating the B cell functions of healthy and lupus patients.
Methods: Human MSCs were isolated from umbilical cords (UC), healthy bone marrow (HBM), and lupus patient bone marrow (LBM). Passages between 4 and 7 were used for these assays. B cells were isolated from peripheral blood of healthy and lupus donors using CD19 micro-beads, then labeled with CFSE for detection of proliferation. B cells were plated at 5×104 per well in 96-well plates, with or without pre-plated MSCs, at the same number, within 24 hours. The cells were incubated at 37°C and 5% CO2 for 96 hours ± stimulation (CpG, CD40L, IL2, and anti-human IgG/IgA/IgG). B cells were then collected and analyzed for proliferation by flow cytometry. Supernatants were collected for detection of antibodies and cytokines via ELISA.
Results: When co-cultured, UC-MSC and HBM-MSC inhibited healthy B cell proliferation better than LBM-MSC. However, only UC-MSC appeared to reduce the proliferation of lupus patient B cells. Regardless of proliferation, healthy B cells cultured in the presences of MSCs experienced increased IgM and IgG production. Supernatants of healthy B cells co-cultured with MSCs also presented increased the levels of IL-6 while having decreased amounts TNF-α when compared to the supernatants of wells with B cells alone.
Conclusion: In our experiments, MSCs obtained from umbilical cords exhibited strong activity in suppressing both healthy and lupus B cell proliferation while MSCs from healthy bone marrow suppressed healthy, but not lupus B cell proliferation. Lupus patient derived MSCs were unable to significantly suppress B cell proliferation from healthy or lupus patients. Furthermore, MSCs from all sources did not inhibit healthy B cell IgG or IgM secretion. These studies aim to improve our understanding of the in vitro effects of MSCs on B cell function in order to predict in vivo efficacy of MSCs to be used in the treatment of SLE.
Disclosure:
E. Collins,
None;
M. Qi,
None;
G. S. Gilkeson,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effects-of-mesenchymal-stem-cells-on-human-b-cell-proliferation/