In the present study, we aimed to evaluate effects of autologous mesenchymal stem cells (MSCs) intravenous administration on the response of B cells, BAFF, APRIL, and their receptors on the surface of B cells at 1, 6, and 12 month follow-up periods in refractory rheumatoid arthritis (RA) patients. Thirteen patients with refractory RA received autologous MSCs. Plasma levels of BAFF and APRIL were measured employing ELISA method, followed by estimating B cell population and BAFFRs evaluation by flow cytometry technique. Gene expression of BAFF, APRIL, and their receptors on B cell surface in PBMCs was evaluated by SYBR Green real-time PCR technique. Plasma concentration of BAFF significantly decreased 1 and 6 months after the MSCT (MSCs Transplantation). Plasma concentration of APRIL significantly decreased 1 month after the MSCT. Percentages of CD19 + B cells in the PBMC population significantly decreased 12 months after the MSCT. Percentages of BR3 + CD19 + B cells and BCMA + CD19 + B cells significantly decreased at the 12th month after the MSCT. The gene expression of BAFF in the PBMC population significantly decreased during 6, and 12 months after the MSCT. The gene expression of APRIL significantly decreased on month 6 after the MSCT. The gene expression of BR3 significantly decreased during 1, 6, and 12 months after the MSCT. The MSCT seems to decrease B cells response because of the reduced production of BAFF and APRIL cytokines and decrease the expression of their receptors on the surface of B cells.