B‐Cell Chronic Lymphocytic Leukemia, a Clonal Disease of B Lymphocytes with Receptors that Vary in Specificity for (Auto)antigens

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Abstract
B-Cell chronic lymphocytic leukemia (B-CLL) is an incurable disease that is relatively common among aging Caucasians. Patients with this leukemia can be divided into prognostic categories using clinical staging parameters, as well as molecular features [presence or absence of IgVH mutations in rearranged VHDJH segments that code for the leukemic B cell's receptor for antigen (BCR)]. In addition, the deduced amino acid structure of the BCRs from patients that fall into different prognostic categories is shared, to varying degrees, within these groups. In this paper, the molecular features of the genes that code for the BCRs of B-CLL patients are reviewed, and these are compared to antibodies of known specificity. These comparisons suggest that the BCRs of many cases resemble autoantibodies, and in some cases, antibodies to microbial antigens. Antigen-binding analyses confirm these impressions, and also indicate that polyreactivity appears to distinguish cases with worse clinical outcomes differ from those with better outcomes. The persistence of autoreactivity and polyreactivity is somewhat surprising, because IgV DNA sequence analyses suggest that many of the B cells that become leukemic have undergone one form or another of receptor editing. Thus, B-CLL appears to be a disease of B-cell clones that have undergone various types of receptor reconfiguration and yet retain inappropriate antigen-binding properties.

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