Marginal Zone B Cells Are Necessary for the Formation of Anti-donor IgG After Allogeneic Sensitization.
| Autor: | Kallarakal MA; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD., Cohen GS, Ibukun FI, Krummey SM |
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| Jazyk: | angličtina |
| Zdroj: | Transplantation [Transplantation] 2024 Jun 01; Vol. 108 (6), pp. 1357-1367. Date of Electronic Publication: 2024 Feb 16. |
| DOI: | 10.1097/TP.0000000000004931 |
| Abstrakt: | Background: The formation of anti-major histocompatibility complex (MHC) antibodies is a significant barrier for many patients awaiting organ transplantation. Patients with preformed anti-MHC antibodies have limited options for suitable donors, and the formation of donor-specific anti-MHC antibodies after transplantation is a harbinger of graft rejection. Despite the recognized importance of anti-MHC antibodies, the mechanisms responsible for the differentiation of B cells after exposure to allogeneic antigens are poorly understood. Methods: To evaluate the differentiation of B cells in response to allogeneic antigen, we used a model of H-2 b C57Bl/6 sensitization with H-2 d antigen. We used a class I MHC tetramer-based approach to identify allogeneic B cells and flow cytometric crossmatch to identify allogeneic IgM and IgG. Results: We found that although the formation of anti-H-2 d IgG was robust, few class-switched B cells and germinal center B cells were formed. Antigen-specific B cells did not express classical memory B-cell markers after sensitization but had an IgM + CD21 + marginal zone B-cell phenotype. The frequency of marginal zone B cells increased after sensitization. Depletion of marginal zone B cells before sensitization or skin grafting resulted in a significant diminution of anti-H-2 d IgG and fewer germinal center B cells. Adoptive transfer experiments revealed that marginal zone B cells more efficiently differentiated into germinal center B cells and anti-donor IgG-producing cells than follicular B cells. Conclusions: These results demonstrate an important role for marginal zone B cells as a reservoir of alloreactive B cells that are activated by allogeneic antigens. Competing Interests: The authors declare no conflicts of interest. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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