In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 10 ( 2022-10-13), p. e0275564-
Abstract:
APRIL (A proliferation inducing ligand) and BLyS (B Lymphocyte Stimulator) are two critical survival factors for B lymphocytes and plasma cells, the main source of alloantibody. We sought to characterize the specific effects of these cytokines in a kidney transplant model of antibody mediated rejection (AMR). We engineered APRIL -/- and BLyS -/- Lewis rats using CRISPR/Cas9. APRIL -/- and BLyS -/- rats were sensitized with Brown Norway (BN) blood (complete MHC mismatch). Twenty-one days following sensitization, animals were harvested and collected tissues were analyzed using flow cytometry, ELISPOT, and immunohistochemistry. Flow cross match and a 3 day mixed lymphocyte reaction (MLR) was performed to assess donor specific antibody (DSA) production and T-cell proliferation, respectively. Sensitized dual knock out Lewis rats (APRIL -/- /BLyS -/- ) underwent kidney transplantation and were sacrificed on day 7 post-transplant. Sensitized BLyS -/- had significant decreases in DSA and cell proliferation compared to WT and APRIL -/- (p 〈 0.02). Additionally, BLyS -/- rats had a significant reduction in IgG secreting cells in splenic marginal zone B lymphocytes, and in cell proliferation when challenged with alloantigen compared to WT and APRIL -/- . Transplanted APRIL -/- /BLyS -/- rodents had significantly less DSA and antibody secreting cells compared to WT (p 〈 0.05); however, this did not translate into a significant difference in AMR seen between groups. In summary, our studies suggest that APRIL and BLyS play a greater role in DSA generation rather than AMR, highlighting the role of cellular pathways that regulate AMR.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0275564
DOI:
10.1371/journal.pone.0275564.g001
DOI:
10.1371/journal.pone.0275564.g002
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10.1371/journal.pone.0275564.g003
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10.1371/journal.pone.0275564.g004
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10.1371/journal.pone.0275564.g005
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10.1371/journal.pone.0275564.g006
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10.1371/journal.pone.0275564.g007
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10.1371/journal.pone.0275564.g008
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10.1371/journal.pone.0275564.g009
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10.1371/journal.pone.0275564.g010
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10.1371/journal.pone.0275564.g011
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10.1371/journal.pone.0275564.g012
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10.1371/journal.pone.0275564.g013
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10.1371/journal.pone.0275564.g014
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10.1371/journal.pone.0275564.g015
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10.1371/journal.pone.0275564.g016
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10.1371/journal.pone.0275564.g017
DOI:
10.1371/journal.pone.0275564.t001
DOI:
10.1371/journal.pone.0275564.s001
DOI:
10.1371/journal.pone.0275564.s002
DOI:
10.1371/journal.pone.0275564.s003
DOI:
10.1371/journal.pone.0275564.s004
DOI:
10.1371/journal.pone.0275564.r001
DOI:
10.1371/journal.pone.0275564.r002
DOI:
10.1371/journal.pone.0275564.r003
DOI:
10.1371/journal.pone.0275564.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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