Mature Naive B Cells Regulate the Outcome of Murine Acute Graft-versus-Host Disease in an IL-10-Independent Manner
•Allogeneic experimental acute graft-versus-host disease (aGVHD) is less severe in in the presence of donor mature I B cells.•aGVHD is as severe in the presence of IL-10-deficient B donor cells as in the total absence of B cells.•Protection from severe aGVHD depends on antigen presentation by donor...
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Veröffentlicht in: | Transplantation and cellular therapy 2022-04, Vol.28 (4), p.181.e1-181.e9 |
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Sprache: | eng |
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Zusammenfassung: | •Allogeneic experimental acute graft-versus-host disease (aGVHD) is less severe in in the presence of donor mature I B cells.•aGVHD is as severe in the presence of IL-10-deficient B donor cells as in the total absence of B cells.•Protection from severe aGVHD depends on antigen presentation by donor B cells but not by regulatory T cells.•Smaller numbers of follicular T cells and higher numbers of effector T cells are associated with the more severe phenotype observed in hematopoietic stem cell transplantation depleted of donor B cells.
Graft-versus-host disease (GVHD) is the main complication of bone marrow transplantation (BMT). CD4+ T lymphocytes are the main effector cells for disease development, but other cell types can determine disease outcome through cytokine production and antigen presentation. B cells are abundant in BMT products and are involved in chronic GVHD immunopathogenesis. However, their role in acute GVHD is still unclear. Here we studied the role of donor resting B cells in a model of acute GVHD. Animals receiving transplants depleted of B cells developed more severe disease, indicating a protective role for B cells. Mice undergoing transplantation with IL-10 knockout B cells developed GVHD as severe as those receiving wild-type B cells. Moreover, mice that received MHC II-deficient B cells, and thus were unable to present antigen to CD4+ T cells, developed as severe GVHD as animals receiving transplants without B cells. This result suggests that the protection provided by mature naive B cells depends on antigen presentation and not on IL-10 production by B cells. Mice who underwent transplantation in the absence of donor B cells exhibited disorganized lymphoid splenic tissue. In addition, donor B cell depletion diminished the follicular T (Tfh)/effector T (Teff) cell ratio, suggesting that protection was correlated with a shift to Tfh differentiation, reducing the number of Teff cells. Importantly, the Tfh/Teff shift impacts disease outcome, with observed proinflammatory cytokine levels and tissue damage in target organs consistent with disease protection. The role of transplanted B cells in the outcome of BMT and the development of acute GVHD merits careful study, given that these cells are abundant in BMT products and are potent modulator and effector cells in the allogeneic response. |
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ISSN: | 2666-6367 2666-6367 |
DOI: | 10.1016/j.jtct.2022.01.004 |