Background We previously reported that IL-6 blockade using an anti-IL6R antibody (mMR16-1) resulted in attenuation of donor-specific antibody (DSA) recall responses in a mouse model of allo-sensitization. However, the mechanism(s) responsible for antibody suppression remain unclear. This study was designed to examine the impact of anti-IL6R on IgG secreting plasma cells in the bone marrows. Methods C57BL/6 mice were pre-sensitized with skin allograft (SG) from a HLA. A2 transgenic mouse. At Day 70 the pre-sensitized mice were re-stimulated with a second HLA.A2+ skin graft. Recall alloantibody responses were monitored by measurement of serum anti-HLA.A2 antibodies. Cells isolated from the spleens and bone marrows were analyzed in FACS examining changes in B-cells and plasma cells and in ELISpot assay for quantitation of IgG secreting plasma cells. Effect of anti-IL6R on antibody forming cell growth was evaluated in a cell proliferation MTT assay using a HLA.A2 producing hybridoma line (PA2.1). Results FACS analysis showed that mMR16-1 had no depleting effect on splenic B-cells. There was a mild reduction in CD38+ CD138+ cell populations in the BM. ELISpot assay showed a significant reduction in IgG+ spot counts in bone marrow cells derived from the mice treated with anti-IL6R compared to that of isotype control mice (p=6.15711E-5). A decrease in IgG+ spot formation in the splenocytes was also seen in the treated mice. However, the difference in IgG+ spot counts between the treated and the control spleens was not statistically significant (p=0.069). Addition of mMR16-1 in ELISpot plate during cell culture significantly decreased IgG spot counts in control bone marrow cells and splenocytes (p<0.01). Cell proliferation MTT assay showed that mMR16-1 significantly suppressed PA2.1 hybridoma growth (p<0.01). Conclusion The data indicate that anti-IL6R antibody may affect the final stage of B cell maturation into plasma cells and/or suppression of antibody forming plasma cells during the development of recall alloantibody responses. Thus, one of the mechanisms by which mMR16-1 attenuates alloantibody responses is consistent with inhibition of a described IL-6 activity as a B/plasma cell growth factor. Future studies are directed to mechanistically illustrate how IL-6R blockage suppresses the long-lived plasma cell compartment, memory B and T cells.