Evaluation of Drug Action on IgM Memory B Cell Survival and Growth In Vitro; -Application for Individualized Immunosuppression after Kidney Transplants-
1Nephrology, Fujita Health University, Toyoake, Aichi, Japan
2Urology, Osaka University, Suita, Osaka, Japan.
Meeting: 2018 American Transplant Congress
Abstract number: D36
Keywords: Antibodies, B cells, Kidney transplantation
Session Information
Session Name: Poster Session D: Immunosuppression Preclinical Studies
Session Type: Poster Session
Date: Tuesday, June 5, 2018
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall 4EF
(Background)
Recently, the establishment of early diagnosis and treatment methods for antibody-mediated rejection (ABMR) has garnered much attention.
Strong immunosuppression including desensitization is accompanied by severe side effects and is known to be necessary for IgG donor-specific HLA antibody (DSA) depletion after antibody production from serum.
(Method)
IgM memory B cells (mBCs) obtained from 10 healthy donors were cultured with IL-21, CpG-ODN, and PBMC supernatant including cytokine and growth factor produced from activated T cells and inflammatory cells in vitro as basic culture medium.
Additionally, AffiniPure F(ab)2 Fragment Goat Anti-human IgM was added to the basic culture medium to induce IgM mBC class-switching through IgM B cell receptor cross-linking.
At each differentiation stage, drug action of everolimus (EVR), cyclosporine (CYA), tacrolimus (TAC), mycophenolic acid (MPA), and prednisolone (PRD) were analyzed.
Dead cells were stained by 7-AAD, and plasma cells (PCs) were identified as CD20 (low) CD38 (high) CD138 (+) cells by FACS.
(Result)
7-AAD expression on cultured cells was significantly upregulated in MPA (400 ng/mL) and PRD (100 ng/mL) groups (P < 0.05, P < 0.05) compared with that in the control group (Fig1-1). The ratio of PCs/total cells in the EVR (1ng/ml, 5 ng/mL) groups were significantly decreased (P < 0.05, P < 0.01) (Fig1-2). IgG expression was significantly decreased in the EVR (5 ng/mL), CYA (400 ng/mL), and TAC (25 ng/mL) groups (P < 0.05, P < 0.05, P < 0.05) (Fig1-3).
(Conclusion)
MPA and PRD suppressed IgM mBC survival; EVR suppressed both its differentiation into PC and class switching into IgG. CYA and TAC suppressed class switching. Therefore, the appropriate administration of immunosuppressive agents on DSA-specific IgM mBC might prevent the differentiation of DSA specific-IgG mBC, which might cause ABMR development (Fig1-4).
CITATION INFORMATION: Matsuda Y., Takahashi K., Imamura R., Nonomura N., Yuzawa Y. Evaluation of Drug Action on IgM Memory B Cell Survival and Growth In Vitro; -Application for Individualized Immunosuppression after Kidney Transplants- Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Matsuda Y, Takahashi K, Imamura R, Nonomura N, Yuzawa Y. Evaluation of Drug Action on IgM Memory B Cell Survival and Growth In Vitro; -Application for Individualized Immunosuppression after Kidney Transplants- [abstract]. https://atcmeetingabstracts.com/abstract/evaluation-of-drug-action-on-igm-memory-b-cell-survival-and-growth-in-vitro-application-for-individualized-immunosuppression-after-kidney-transplants/. Accessed May 16, 2025.« Back to 2018 American Transplant Congress