title: The costimulatory immunogen LPS induces the B-Cell clones that infiltrate transplanted human kidneys.
abstract: The mechanism of chronic rejection of transplanted human kidneys is unknown. An understanding of this process is important because, chronic rejection ultimately leads to loss of the kidney allograft in most transplants. One feature of chronic rejection is the infiltration of ectopic B-cell clusters that are clonal into the transplanted kidney. We now show that the antibodies produced by these B-cells react strongly with the core carbohydrate region of LPS. Since LPS is a costimulatory immunogen that can react with both the B-cell receptor (BCR) and the Toll-like receptor 4 (TLR4), these results suggest a mechanism for the selective pressure that leads to clonality of these B-cell clusters and opens the possibility that infection and the attendant exposure to LPS plays a role in the chronic rejection of human kidney transplants. If confirmed by clinical studies, these results suggest that treating patients with signs of chronic rejection with antibiotics may improve kidney allograft survival.
authors.affiliation: Departments of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Grover
authors.forename: Julong
authors.initials: J
authors.lastname: Cheng
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Peng
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Jones
authors.forename: Diana I
authors.initials: DI
authors.lastname: Ruiz
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Ulevitch
authors.forename: John I
authors.initials: JI
authors.lastname: Glass
authors.forename: Edward A
authors.initials: EA
authors.lastname: Dennis
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Salomon
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lerner
mesh_terms: D000918:Antibody Specificity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002908:Chronic Disease; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000276:immunology* / Q000378:metabolism; D016030:Kidney Transplantation / Q000379:methods*; D008070:Lipopolysaccharides / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000097:blood / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell; D057127:Single-Chain Antibodies; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4