Allo-Specific Humoral Responses: New Methods for Screening Donor-Specific Antibody and Characterization of HLA-Specific Memory B Cells.

dc.contributor.author

Song, Shengli

dc.contributor.author

Manook, Miriam

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Kwun, Jean

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Jackson, Annette M

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Knechtle, Stuart J

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Kelsoe, Garnett

dc.date.accessioned

2022-11-01T19:32:55Z

dc.date.available

2022-11-01T19:32:55Z

dc.date.issued

2021-01

dc.date.updated

2022-11-01T19:32:49Z

dc.description.abstract

Antibody-mediated allograft rejection (AMR) causes more kidney transplant failure than any other single cause. AMR is mediated by antibodies recognizing antigens expressed by the graft, and antibodies generated against major histocompatibility complex (MHC) mismatches are especially problematic. Most research directed towards the management of clinical AMR has focused on identifying and characterizing circulating donor-specific HLA antibody (DSA) and optimizing therapies that reduce B-cell activation and/or block antibody secretion by inhibiting plasmacyte survival. Here we describe a novel set of reagents and techniques to allow more specific measurements of MHC sensitization across different animal transplant models. Additionally, we have used these approaches to isolate and clone individual HLA-specific B cells from patients sensitized by pregnancy or transplantation. We have identified and characterized the phenotypes of individual HLA-specific B cells, determined the V(D)J rearrangements of their paired H and L chains, and generated recombinant antibodies to determine affinity and specificity. Knowledge of the BCR genes of individual HLA-specific B cells will allow identification of clonally related B cells by high-throughput sequence analysis of peripheral blood mononuclear cells and permit us to re-construct the origins of HLA-specific B cells and follow their somatic evolution by mutation and selection.

dc.identifier.issn

1664-3224

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1664-3224

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https://hdl.handle.net/10161/26169

dc.language

eng

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Frontiers Media SA

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Frontiers in immunology

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10.3389/fimmu.2021.705140

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B-Lymphocyte Subsets

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Cells, Cultured

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Cell Line

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Clone Cells

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Animals

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Mice, Inbred C57BL

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Macaca mulatta

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Humans

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Mice

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Immunoglobulin G

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beta 2-Microglobulin

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RNA, Guide

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Isoantibodies

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Histocompatibility Antigens

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HLA Antigens

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Indicators and Reagents

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Skin Transplantation

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Lymphocyte Activation

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Models, Animal

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Specific Pathogen-Free Organisms

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Antibody Specificity

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Species Specificity

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Graft Rejection

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Gene Rearrangement, B-Lymphocyte

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Immunologic Memory

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Genes, Reporter

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Female

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V(D)J Recombination

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Clonal Evolution

dc.title

Allo-Specific Humoral Responses: New Methods for Screening Donor-Specific Antibody and Characterization of HLA-Specific Memory B Cells.

dc.type

Journal article

duke.contributor.orcid

Kwun, Jean|0000-0002-8563-5472

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Jackson, Annette M|0000-0003-2648-2944

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Knechtle, Stuart J|0000-0002-1625-385X

duke.contributor.orcid

Kelsoe, Garnett|0000-0002-8770-040X

pubs.begin-page

705140

pubs.organisational-group

Duke

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School of Medicine

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Immunology

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Medicine

pubs.organisational-group

Surgery

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Medicine, Nephrology

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Surgery, Abdominal Transplant Surgery

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Surgery, Surgical Sciences

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Duke Cancer Institute

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Duke Clinical Research Institute

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Duke Human Vaccine Institute

pubs.publication-status

Published

pubs.volume

12

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