B‐cell receptor epitope recognition correlates with the clinical course of chronic lymphocytic leukemia

Abstract

B-cell receptors (BCRs) and their recognition of specific epitopes may play a pivotal role in the development and progression of chronic lymphocytic leukemia (CLL). In this study, the authors set up a model system to explore epitope reactivity and its clinical relevance in CLL. Epitope-mimicking peptides were selected from phage display libraries on 6 CLL BCRs from randomly chosen patients. The binding of the 6 index epitope mimics was evaluated in a set of 100 unrelated CLL samples. Epitope recognition patterns were correlated with the clinical course of the disease. Surprisingly, all CLL samples recognized 1 or several index epitopes, and some revealed marked polyreactivity. Patients with CLL who expressed BCRs that reacted with ≥5 epitope mimics had a significantly worse clinical course than less polyreactive patients (median time to first treatment, 24 months vs 102 months). This effect was independent of otherwise known prognostic markers. The authors introduced a system with which to model epitope reactivity of CLL BCRs without previous knowledge of potential antigens. The findings indicated that a polyreactive epitope recognition pattern may be a determinant of an aggressive clinical course in this disease. This further emphasizes the functional and prognostic relevance of BCR epitope recognition in CLL.