PMID- 37034637
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240328
DP  - 2023 Jun 24
TI  - B cell and antibody targeting of transplant alloantigen epitopes is supported by 
      both self and allo-recognition.
LID - 2023.03.31.534734 [pii]
LID - 10.1101/2023.03.31.534734 [doi]
AB  - Donor-specific antibody (DSA) responses against human leukocyte antigen (HLA) 
      proteins mismatched between kidney transplant donors and recipients cause 
      allograft loss. Using single-cell, molecular, structural, and proteomic 
      techniques, we profiled the HLA-specific (alloreactive) B cell response in kidney 
      and blood of a transplant recipient with antibody-mediated rejection (AMR). We 
      identified 14 distinct alloreactive B cell lineages, which spanned the rejected 
      organ and blood and expressed high-affinity anti-donor HLA-specific B cell 
      receptors, many of which were clonally linked to circulating DSA. The 
      alloreactive B cell response was focused on exposed, solvent-accessible 
      mismatched HLA residues, while also demonstrating extensive contacts with 
      self-HLA residues. Consistent with structural evidence of self-recognition, 
      measurable self-reactivity by donor-specific B cells was common and positively 
      correlated with anti-donor affinity maturation. Thus, allo- and self-reactive 
      signatures appeared to converge, suggesting that during AMR, the recognition of 
      non-self and breaches of tolerance conspire to produce a pathogenic 
      donor-specific adaptive response.
FAU - Killian, John T
AU  - Killian JT
AUID- ORCID: 0000-0002-3702-9005
FAU - King, Rodney G
AU  - King RG
FAU - Kizziah, James L
AU  - Kizziah JL
FAU - Fucile, Christopher F
AU  - Fucile CF
FAU - Diaz-Avalos, Ruben
AU  - Diaz-Avalos R
FAU - Qiu, Shihong
AU  - Qiu S
FAU - Silva-Sanchez, Aaron
AU  - Silva-Sanchez A
FAU - Mousseau, Betty J
AU  - Mousseau BJ
FAU - Macon, Kevin J
AU  - Macon KJ
FAU - Callahan, Amanda R
AU  - Callahan AR
FAU - Yang, Guang
AU  - Yang G
FAU - Hossain, M Emon
AU  - Hossain ME
FAU - Akther, Jobaida
AU  - Akther J
FAU - Houp, Julie A
AU  - Houp JA
FAU - Rosenblum, Frida D
AU  - Rosenblum FD
FAU - Porrett, Paige M
AU  - Porrett PM
FAU - Ong, Song C
AU  - Ong SC
FAU - Kumar, Vineeta
AU  - Kumar V
FAU - Saphire, Erica Ollmann
AU  - Saphire EO
FAU - Kearney, John F
AU  - Kearney JF
FAU - Randall, Troy D
AU  - Randall TD
FAU - Rosenberg, Alexander F
AU  - Rosenberg AF
FAU - Green, Todd J
AU  - Green TJ
FAU - Lund, Frances E
AU  - Lund FE
LA  - eng
GR  - P30 AI027767/AI/NIAID NIH HHS/United States
GR  - T32 AI007051/AI/NIAID NIH HHS/United States
GR  - U19 AI142737/AI/NIAID NIH HHS/United States
GR  - T32 DK007545/DK/NIDDK NIH HHS/United States
GR  - S10 OD024978/OD/NIH HHS/United States
GR  - P30 CA013148/CA/NCI NIH HHS/United States
PT  - Preprint
DEP - 20230624
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
PMC - PMC10081326
EDAT- 2023/04/11 06:00
MHDA- 2023/04/11 06:01
PMCR- 2023/06/26
CRDT- 2023/04/10 04:11
PHST- 2023/04/11 06:00 [pubmed]
PHST- 2023/04/11 06:01 [medline]
PHST- 2023/04/10 04:11 [entrez]
PHST- 2023/06/26 00:00 [pmc-release]
AID - 2023.03.31.534734 [pii]
AID - 10.1101/2023.03.31.534734 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2023 Jun 24:2023.03.31.534734. doi: 
      10.1101/2023.03.31.534734.