Article Text

AB0224 Oaz regulate B-cell functions through the inhibition of CCL2 expression in mesenchymal stem cells
  1. X. Feng,
  2. N. Che,
  3. Y. Liu,
  4. D. Wang,
  5. L. Sun
  1. Rheumatology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China


Background Mesenchymal stem cells (MSCs) had been indicated to exert suppressive effects on B-cell proliferation and differentiation through released humoral factor(s) yet to be defined, which is impaired in patients with systemic lupus erythematosus (SLE). Our data showed that Olf1/EBF associated zinc finger protein (OAZ), a recently indentified lupus susceptibility gene involving in the production of antinuclear antibody (ANA), highly expressed in MSCs especially those from SLE patients, suggesting a role of this gene in the regulation of MSC-B cell functions.

Objectives To find out how OAZ act to affect MSC-B cell regulations.

Methods Splenic B cells from MRL/lpr lupus mice were purified using anti-CD43 antibody and immunomagnetic beads. MSCs from bone marrow of SLE patients or healthy donors were isolated and expanded by culturing for 3-4 passages. MSCs (1: 10) were seeded in wells 6-8 hours before adding B cells, then co-cultured for 3 days with lipopolysaccharide in a tissue culture incubator. The effect of MSC on the proliferation of B cells was evaluated by using BrdU assay, and the B-cell differentiation was established using flow cytometry based on the expression of CD19 and CD138. Some of the wells were incubated with siRNAs targeting human OAZ (using non-targeting sequence as negative control) or anti-CCL2 neutralizing antibody (using isotype Ig as control). Cultured supernatants were harvested and measured for ANA as well as IgG levels by ELISA.

Results Compared to normal MSCs, high percentages of BrdU positive cells and CD19+CD138+ cells were detected when mouse B cells were co-cultured with MSCs from SLE patients. Silencing of human OAZ partially restored the ability of SLE MSCs to inhibit B cells proliferation and differentiation by 51.2% and 69.4% respectively. Meanwhile, a decline of ANA and total IgG was also observed. The level of CCL2, a MSC-derived chemokine involved in plasmablast proliferation that dramatically lowered in supernatants of SLE MSCs–mouse B cells co-cultures, was elevated after OAZ silencing. When anti-CCL2 antibody was added to the co-culture system with OAZ silenced, percentages of BrdU positive cells and CD19+CD138+ cells were both significantly increased.

Conclusions Elevated expression of OAZ could weaken the inhibitory function of MSCs on B cells through the reduction of MSC-derived CCL2 secretion, thus contribute to the onset of SLE.

Disclosure of Interest None Declared

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