title: Self-antigen recognition by follicular lymphoma B-cell receptors.
abstract: Follicular lymphoma is a monoclonal B-cell malignancy with each patient's tumor expressing a unique cell surface immunoglobulin (Ig), or B-cell receptor (BCR), that can potentially recognize antigens and/or transduce signals into the tumor cell. Here we evaluated the reactivity of tumor derived Igs for human tissue antigens. Self-reactivity was observed in 26% of tumor Igs (25 of 98). For one follicular lymphoma patient, the recognized self-antigen was identified as myoferlin. This patient's tumor cells bound recombinant myoferlin in proportion to their level of BCR expression, and the binding to myoferlin was preserved despite ongoing somatic hypermutation of Ig variable regions. Furthermore, BCR-mediated signaling was induced after culture of tumor cells with myoferlin. These results suggest that antigen stimulation may provide survival signals to tumor cells and that there is a selective pressure to preserve antigen recognition as the tumor evolves.
authors.affiliation: Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Kacey L
authors.initials: KL
authors.lastname: Sachen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Strohman
authors.forename: Jonathan
authors.initials: J
authors.lastname: Singletary
authors.forename: Ash A
authors.initials: AA
authors.lastname: Alizadeh
authors.forename: Nicole H
authors.initials: NH
authors.lastname: Kattah
authors.forename: Chen
authors.initials: C
authors.lastname: Lossos
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Mellins
authors.forename: Shoshana
authors.initials: S
authors.lastname: Levy
authors.forename: Ronald
authors.initials: R
authors.lastname: Levy
mesh_terms: D000912:Antibodies, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004273:DNA, Neoplasm / Q000235:genetics; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007368:Interferometry; D008224:Lymphoma, Follicular / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D009124:Muscle Proteins / Q000235:genetics / Q000276:immunology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D011499:Protein Processing, Post-Translational; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D000912:Antibodies, Neoplasm; D001324:Autoantigens; D002135:Calcium-Binding Proteins; D004273:DNA, Neoplasm; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; C415584:MYOF protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins; C069329:RPS6KA1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa