title: Ectopic B-cell clusters that infiltrate transplanted human kidneys are clonal.
abstract: B cells and their immunoglobulin products participate in allograft rejection of transplanted human kidneys in which an interesting feature is the presence of a germinal center like B-cell clusters in the allograft. We report here that the immunoglobulin repertoires of these infiltrating B cells are highly restricted and the B cells within a cluster are clonal. Antibody libraries made from the infiltrating B cells of individual patients unexpectedly revealed that each patient utilizes a particular set of dominant germ line genes as well as dominant complementarity determining region 3. Comparison of kidney and peripheral blood from the same patient showed that the immunoglobulin genes from both compartments had dominant clones, but they differed. The lymphocytes that infiltrate the kidneys express the immunoglobulin gene somatic recombination machinery usually restricted to highly activated lymphocytes in germinal centers and lymphomas. An analogy can be made between the inescapable antigenic drive in chronic infection versus that in an allograft, both of which may lead to emergence of dominant B-cell clones and even lymphoid malignancy.
authors.affiliation: Department of Molecular Biology and Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Julong
authors.initials: J
authors.lastname: Cheng
authors.forename: Ali
authors.initials: A
authors.lastname: Torkamani
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Grover
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Jones
authors.forename: Diana I
authors.initials: DI
authors.lastname: Ruiz
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: Michael M
authors.initials: MM
authors.lastname: Quigley
authors.forename: F Wesley
authors.initials: FW
authors.lastname: Hall
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Salomon
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lerner
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001483:Base Sequence; D002465:Cell Movement / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D022801:Complementarity Determining Regions / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology*; D005803:Genes, Immunoglobulin / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000166:cytology* / Q000276:immunology; D016030:Kidney Transplantation; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D000906:Antibodies; D022801:Complementarity Determining Regions