*Purpose: IgG and IgM memory B cells (mBCs) corresponding donor-specific antigen are closely involved in the activation of humoral immunity against transplanted grafts. Therefore, it is expected that immunosuppression targeting both donor antigen-specific IgG and IgM mBC survival and growth will play important roles in the prevention of antibody-mediated rejection (AMR) development.

*Methods: Peripheral blood mononuclear cells obtained from healthy donors (n = 5) are incubated with IL-21, IL-4, CpG-ODN, anti-CD40 ligand, PHA-L, and PMA containing AffiniPure F(ab’)₂ Fragment Goat Anti-Human IgM, Fc5μ fragment-specific or AffiniPure F(ab’)₂ Fragment Goat Anti-Human IgG, and F(ab’)₂ fragment specific for B cell receptor (BCR) cross-linking in vitro. We compared the effects of signaling via IgG or IgM type B cell receptor on B cell receptor-mediated mTOR phosphorylation signal in IgG mBCs and IgM naïve-B cells, mBCs in vitro by using phospho-mTOR ELISA kit. Additionally, We compared the effects of everolimus (EVR; 0, 2.5, 5, and 10 ng/mL) on IgM mBC survival, proliferation, and class switching into IgG, and IgG mBC survival, proliferation, and differentiation into plasma cell in vitro.

*Results: Signaling through the IgG BCR mediated mTOR phosphorylation signal more strongly and long-term persistence compared to IgM BCR in vitro findings. In addition, EVR inhibited the IgM mBC survival, proliferating more strongly than IgG, and did not inhibit the IgG mBC differentiation into plasma cells at the abovementioned administration concentration.

*Conclusions: Our findings might indicate IgM mBCs are sensitive to the less mTOR inhibitor administration than to IgG mBCs, and mTOR administration before IgM mBC class-switch into IgG- might prevent IgG PCs development more efficiently and its application will lead to an effective administration method to suppress the development of AMR and improve the prognosis of transplanted grafts after further elucidation of the effects of mTOR inhibitor on regulatory cells.

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