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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.
AuthorsKacey L Sachen, Michael J Strohman, Jonathan Singletary, Ash A Alizadeh, Nicole H Kattah, Chen Lossos, Elizabeth D Mellins, Shoshana Levy, Ronald Levy
JournalBlood (Blood) Vol. 120 Issue 20 Pg. 4182-90 (Nov 15 2012) ISSN: 1528-0020 [Electronic] United States
PMID23024238 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Neoplasm
  • Autoantigens
  • Calcium-Binding Proteins
  • DNA, Neoplasm
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • MYOF protein, human
  • Membrane Proteins
  • Muscle Proteins
  • Neoplasm Proteins
  • Receptors, Antigen, B-Cell
  • Recombinant Proteins
  • RPS6KA1 protein, human
  • Ribosomal Protein S6 Kinases, 90-kDa
Topics
  • Antibodies, Neoplasm (chemistry, genetics, immunology)
  • Autoantigens (genetics, immunology)
  • Autoimmunity
  • Calcium-Binding Proteins (genetics, immunology)
  • Cell Line, Tumor
  • Cell Survival
  • DNA, Neoplasm (genetics)
  • Glycosylation
  • Humans
  • Immunoglobulin G (chemistry, genetics, immunology)
  • Immunoglobulin Heavy Chains (genetics)
  • Immunoglobulin Light Chains (genetics)
  • Interferometry
  • Lymphoma, Follicular (immunology)
  • Membrane Proteins (genetics, immunology)
  • Muscle Proteins (genetics, immunology)
  • Neoplasm Proteins (genetics, immunology)
  • Protein Processing, Post-Translational
  • Receptors, Antigen, B-Cell (immunology)
  • Recombinant Proteins (genetics, immunology)
  • Ribosomal Protein S6 Kinases, 90-kDa (metabolism)
  • Tumor Microenvironment (immunology)

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