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Self-antigen recognition by follicular lymphoma B-cell receptors

Kacey L. Sachen, Michael J. Strohman, Jonathan Singletary, Ash A. Alizadeh, Nicole H. Kattah, Chen Lossos, Elizabeth D. Mellins, Shoshana Levy and Ronald Levy

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.

  • Submitted May 1, 2012.
  • Accepted September 23, 2012.
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