title: Chronic lymphocytic leukemia monitoring with a Lamprey idiotope-specific antibody.
abstract: For antigen recognition, lampreys use leucine-rich repeats (LRR) instead of immunoglobulin V-(D)-J domains to generate variable lymphocyte receptors (VLR) of three types, VLRA, VLRB, and VLRC. VLRB-bearing lymphocytes respond to immunization with proliferation and differentiation into plasmacytes that secrete multivalent VLRB antibodies. Here we immunized lampreys with B cells from patients with chronic lymphocytic leukemia (CLL) to generate recombinant monoclonal VLRB antibodies, one of which, VLR39, was specific for the donor CLL cells. The target epitope of VLR39 was shown to be the complementarity determining region 3 (CDR3) of the heavy chain variable region (VH) of the B cell receptor. Using this antibody to monitor the CLL donor after chemo-immunotherapy-induced remission, we detected VLR39(+) B cells in the patient 51 months later, before significant increase in lymphocyte count or CD5(+) B cells. This indication of reemergence of the leukemic clone was verified by VH sequencing. Lamprey antibodies can exhibit exquisite specificity for a protein epitope, a CLL signature VH CDR3 sequence in this case, and offer a rapid strategy for generating anti-idiotype antibodies for early detection of leukemia recurrence.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Nakahara
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Brantley R
authors.initials: BR
authors.lastname: Herrin
authors.affiliation: Department of Pediatric Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Alder
authors.affiliation: The Feinstein Institute for Medical Research, North Shore-Long Island Jewish (LIJ) Health System, Manhasset, NY, 11030, USA.
authors.forename: Rosa
authors.initials: R
authors.lastname: Catera
authors.affiliation: The Feinstein Institute for Medical Research, North Shore-Long Island Jewish (LIJ) Health System, Manhasset, NY, 11030, USA.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Yan
authors.affiliation: The Feinstein Institute for Medical Research, North Shore-Long Island Jewish (LIJ) Health System, Manhasset, NY, 11030, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Chiorazzi
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Max D
authors.initials: MD
authors.lastname: Cooper
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D000918:Antibody Specificity; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology; D022801:Complementarity Determining Regions / Q000235:genetics*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology; D007798:Lampreys / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell
keywords: B cell receptor; chronic lymphocytic leukemia; idiotype; lamprey antibodies; tumor cell markers