Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection

Asano, Yuta; Daccache, Joe; Jain, Dharmendra; Ko, Kichul; Kinloch, Andrew J; Veselits, Margaret; Wolfgeher, Donald J.; Chang, Anthony; Josephson, Michelle A.; Cunningham, Patrick N.; Tambur, Anat R.; Khan, Aly A.; Pillai, Shiv; Chong, Anita S.

doi:10.1038/s41467-021-24615-6

Cited by 41 publications

(54 citation statements)

References 94 publications

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“…The presence of donor-specific Abs (DSAs) inside the graft differs from that in peripheral blood in chronic lung allograft dysfunction (CLAD) ( 33 ), aligning with our finding that absence of systemic DSAs does not infer that BALF IgGs are not DSAs. Accumulating data highlight an autoreactive or polyreactive repertoire of intragraft Ig, as documented in cardiac allograft vasculopathy ( 36 ) or Ab-mediated rejection after kidney transplantation ( 37 ). The assessment of BALF Ig specificity and its overlap with the B cell receptor repertoire of MZB1 + cells will thus constitute a focus area for future investigations.…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation

Smirnova¹,

Riemondy²,

Bueno³

et al. 2022

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation

Smirnova¹,

Riemondy²,

Bueno³

et al. 2022

JCI Insight

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“…Moreover, they showed that this type of B cell is involved in the loss of peripheral tolerance to organ-restricted antigens. Based on their inflammatory state, and antibody specificity, Bin cells connect innate and adaptive immunity to drive local inflammation [ 28 , 29 ].…”

Section: Immunity Aspect Of Non-hla Antibodiesmentioning

confidence: 99%

Non-HLA Antibodies in Kidney Transplantation: Immunity and Genetic Insights

et al. 2022

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The polymorphic human leukocyte antigen (HLA) system has been considered the main target for alloimmunity, but the non-HLA antibodies and autoimmunity have gained importance in kidney transplantation (KT). Apart from the endothelial injury, secondary self-antigen exposure and the presence of polymorphic alloantigens, respectively, auto- and allo- non-HLA antibodies shared common steps in their development, such as: antigen recognition via indirect pathway by recipient antigen presenting cells, autoreactive T cell activation, autoreactive B cell activation, T helper 17 cell differentiation, loss of self-tolerance and epitope spreading phenomena. Both alloimmunity and autoimmunity play a synergic role in the formation of non-HLA antibodies, and the emergence of transcriptomics and genome-wide evaluation techniques has led to important progress in understanding the mechanistic features. Among them, non-HLA mismatches between donors and recipients provide valuable information regarding the role of genetics in non-HLA antibody immunity and development.

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“…For patients awaiting transplantation, HLA sensitization can dramatically limit the number of compatible donors, and the formation of anti-donor HLA antibodies after transplantation leads to graft rejection and loss (5,6). Thus, further mechanistic insight into the cellular and molecular pathways that lead to HLA sensitization could lead to improved risk stratification of patients prior to transplant and pathwayspecific treatments for graft rejection (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Marginal Zone B Cells are Necessary for the Formation of Anti-Donor IgG After Allogeneic Sensitization

Kallarakal¹,

Cohen²,

Ibukun³

et al. 2022

Preprint

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The formation of anti-MHC antibody is a significant barrier to improved outcomes in organ transplantation. Patients with pre-formed anti-HLA antibodies have limited options for suitable donors, and the formation of donor-specific anti-HLA antibodies after transplantation is a harbinger of graft rejection. Despite the recognized importance of anti-HLA antibodies, the mechanisms responsible for the differentiation of B cells after exposure to allogeneic antigen are poorly understood. In order to evaluate the differentiation of B cells in response to allogeneic antigen, we used a model of H-2b C57/Bl6 sensitization with H-2d antigen. We found that although the formation of anti-H-2d IgG was robust, few class switched B cells and germinal center B cells were formed. Sensitization induced weak expression of classical memory B cell markers, but we observed populations of CD21+ and IRF4+ B cells, that corresponded to an increase in the frequency of marginal zone phenotype B cells after sensitization. Depletion of marginal zone B cells prior to sensitization resulted in a significant dimunition of anti-H-2d IgG and also fewer germinal center B cells. These results demonstrate a previously unappreciated role for marginal zone B cells as a reservoir of alloreactive B cells that are activated by allogeneic antigen.

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Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection

Cited by 41 publications

References 94 publications

Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation

Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation

Non-HLA Antibodies in Kidney Transplantation: Immunity and Genetic Insights

Marginal Zone B Cells are Necessary for the Formation of Anti-Donor IgG After Allogeneic Sensitization

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