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

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

doi:10.1038/s41467-021-24615-6

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

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

^*Corresponding author for this work

Surgery, Transplant Surgery Division

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Intrarenal B cells in human renal allografts indicate transplant recipients with a poor prognosis, but how these cells contribute to rejection is unclear. Here we show using single-cell RNA sequencing that intrarenal class-switched B cells have an innate cell transcriptional state resembling mouse peritoneal B1 or B-innate (Bin) cells. Antibodies generated by Bin cells do not bind donor-specific antigens nor are they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently express antibodies reactive with either renal-specific or inflammation-associated antigens. Furthermore, local antigens can drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. These data show a mechanism of human inflammation in which a breach in organ-restricted tolerance by infiltrating innate-like B cells drives local tissue destruction.

Original language	English (US)
Article number	4372
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-24615-6
State	Published - Dec 2021

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Asano, Y., Daccache, J., Jain, D., Ko, K., Kinloch, A., Veselits, M., Wolfgeher, D., Chang, A., Josephson, M., Cunningham, P., Tambur, A., Khan, A. A., Pillai, S., Chong, A. S., & Clark, M. R. (2021). Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection. Nature communications, 12(1), [4372]. https://doi.org/10.1038/s41467-021-24615-6

Asano, Yuta ; Daccache, Joe ; Jain, Dharmendra ; Ko, Kichul ; Kinloch, Andrew ; Veselits, Margaret ; Wolfgeher, Donald ; Chang, Anthony ; Josephson, Michelle ; Cunningham, Patrick ; Tambur, Anat ; Khan, Aly A. ; Pillai, Shiv ; Chong, Anita S. ; Clark, Marcus R. / Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection. In: Nature communications. 2021 ; Vol. 12, No. 1.

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title = "Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection",

abstract = "Intrarenal B cells in human renal allografts indicate transplant recipients with a poor prognosis, but how these cells contribute to rejection is unclear. Here we show using single-cell RNA sequencing that intrarenal class-switched B cells have an innate cell transcriptional state resembling mouse peritoneal B1 or B-innate (Bin) cells. Antibodies generated by Bin cells do not bind donor-specific antigens nor are they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently express antibodies reactive with either renal-specific or inflammation-associated antigens. Furthermore, local antigens can drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. These data show a mechanism of human inflammation in which a breach in organ-restricted tolerance by infiltrating innate-like B cells drives local tissue destruction.",

author = "Yuta Asano and Joe Daccache and Dharmendra Jain and Kichul Ko and Andrew Kinloch and Margaret Veselits and Donald Wolfgeher and Anthony Chang and Michelle Josephson and Patrick Cunningham and Anat Tambur and Khan, {Aly A.} and Shiv Pillai and Chong, {Anita S.} and Clark, {Marcus R.}",

note = "Funding Information: This work was supported by the NIH Autoimmunity Centers of Excellence and NIH grant U19 AI082724 (M.R.C. and S.P.) and NIH grant AI148705 (M.R.C. and A.C.). The authors acknowledge Mayo Clinic Medical Genome Facility Proteomics Core for generating raw mass-spectrometry data. Y.A. also acknowledges Heiwa Nakajima Foundation for its support. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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doi = "10.1038/s41467-021-24615-6",

language = "English (US)",

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Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection. / Asano, Yuta; Daccache, Joe; Jain, Dharmendra; Ko, Kichul; Kinloch, Andrew; Veselits, Margaret; Wolfgeher, Donald; Chang, Anthony; Josephson, Michelle; Cunningham, Patrick; Tambur, Anat; Khan, Aly A.; Pillai, Shiv; Chong, Anita S.; Clark, Marcus R.

In: Nature communications, Vol. 12, No. 1, 4372, 12.2021.

Research output: Contribution to journal › Article › peer-review

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AU - Asano, Yuta

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AU - Jain, Dharmendra

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AU - Kinloch, Andrew

AU - Veselits, Margaret

AU - Wolfgeher, Donald

AU - Chang, Anthony

AU - Josephson, Michelle

AU - Cunningham, Patrick

AU - Tambur, Anat

AU - Khan, Aly A.

AU - Pillai, Shiv

AU - Chong, Anita S.

AU - Clark, Marcus R.

N1 - Funding Information: This work was supported by the NIH Autoimmunity Centers of Excellence and NIH grant U19 AI082724 (M.R.C. and S.P.) and NIH grant AI148705 (M.R.C. and A.C.). The authors acknowledge Mayo Clinic Medical Genome Facility Proteomics Core for generating raw mass-spectrometry data. Y.A. also acknowledges Heiwa Nakajima Foundation for its support. Publisher Copyright: © 2021, The Author(s).

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N2 - Intrarenal B cells in human renal allografts indicate transplant recipients with a poor prognosis, but how these cells contribute to rejection is unclear. Here we show using single-cell RNA sequencing that intrarenal class-switched B cells have an innate cell transcriptional state resembling mouse peritoneal B1 or B-innate (Bin) cells. Antibodies generated by Bin cells do not bind donor-specific antigens nor are they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently express antibodies reactive with either renal-specific or inflammation-associated antigens. Furthermore, local antigens can drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. These data show a mechanism of human inflammation in which a breach in organ-restricted tolerance by infiltrating innate-like B cells drives local tissue destruction.

AB - Intrarenal B cells in human renal allografts indicate transplant recipients with a poor prognosis, but how these cells contribute to rejection is unclear. Here we show using single-cell RNA sequencing that intrarenal class-switched B cells have an innate cell transcriptional state resembling mouse peritoneal B1 or B-innate (Bin) cells. Antibodies generated by Bin cells do not bind donor-specific antigens nor are they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently express antibodies reactive with either renal-specific or inflammation-associated antigens. Furthermore, local antigens can drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. These data show a mechanism of human inflammation in which a breach in organ-restricted tolerance by infiltrating innate-like B cells drives local tissue destruction.

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

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