title: Expansion of polyreactive B cells cross-reactive to HLA and self in the blood of a patient with kidney graft rejection.
abstract: Antibody rejection is often accompanied by nondonor HLA specific antibodies (NDSA) and self-reactive antibodies that develop alongside donor-specific antibodies (DSA). To determine the source of these antibodies, we immortalized 107 B-cell clones from a kidney transplant recipient with humoral rejection. Two of these clones reacted to HLA class I or MICA. Both clones were also reactive to self-antigens and a lysate of a kidney cell line, hence revealing a pattern of polyreactivity. Monoclonality was verified by the identification of a single rearranged immunoglobulin heavy chain variable region (VH) sequence for each clone. By tracking their unique CDR3 sequence, we found that one such polyreactive clone was highly expanded in the patient blood, representing ~0.2% of circulating B cells. The VH sequence of this clone showed evidence of somatic mutations that were consistent with its memory phenotype and its expansion. Lastly, the reactivity of the expanded polyreactive B-cell clone was found in the patient serum at time of rejection. In conclusion, we provide here proof of principle at the clonal level that human antibodies can cross-react to HLA and self. Our findings strongly suggest that polyreactive antibodies contribute to DSA, NDSA as well as autoantibodies, in transplant recipients.
authors.affiliation: Department of Surgery, Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Porcheray
authors.forename: J
authors.initials: J
authors.lastname: DeVito
authors.forename: Y
authors.initials: Y
authors.lastname: Helou
authors.forename: I
authors.initials: I
authors.lastname: Dargon
authors.forename: J W
authors.initials: JW
authors.lastname: Fraser
authors.forename: P
authors.initials: P
authors.lastname: Nobecourt
authors.forename: J
authors.initials: J
authors.lastname: Ferdman
authors.forename: S
authors.initials: S
authors.lastname: Germana
authors.forename: T C
authors.initials: TC
authors.lastname: Girouard
authors.forename: T
authors.initials: T
authors.lastname: Kawai
authors.forename: S L
authors.initials: SL
authors.lastname: Saidman
authors.forename: W
authors.initials: W
authors.lastname: Wong
authors.forename: R B
authors.initials: RB
authors.lastname: Colvin
authors.forename: C
authors.initials: C
authors.lastname: Leguern
authors.forename: E
authors.initials: E
authors.lastname: Zorn
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*
chemical_list: D006680:HLA Antigens