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    Kacey Layn Sachen.
    Follicular lymphoma (FL) is a monoclonal B cell malignancy and each tumor expresses a unique cell surface immunoglobulin (Ig) molecule that can potentially recognize antigens and/or transduce signals into the tumor cell. There is evidence that the functions of antigen binding and signaling are important for maintaining the survival of the FL tumor cells. The Ig variable region genes of these tumors undergo somatic hypermutation and yet functional Ig molecules are preserved. Additionally, the distribution of replacement and silent mutations within the Ig V genes implies a selective force to preserve their ability to bind antigens. We screened the tumor-derived Ig from a large collection of FL tumors and observed a high frequency of reactivity against human tissue antigens. For one FL patient, the recognized self-antigen was identified as myoferlin. This patient's tumor cells bound myoferlin in proportion to their level of surface Ig, and the binding to myoferlin was preserved despite ongoing IgV region somatic mutation. These findings indicate that FL may often be driven by auto-antigens. The preservation of antigen recognition despite ongoing somatic hypermutation suggests a functional positive selective pressure for tumors to maintain the ability to recognize antigens.
    Digital Access 2012
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