Similar characteristics of the CDR3 of VH1-69/DP-10 rearrangements in normal human peripheral blood and chronic lymphocytic leukaemia B cells

Abstract

The variable heavy chain (V_H) gene segment V_H1-69/DP-10 has been shown to be over-represented in B-cell chronic lymphocytic leukaemia (CLL). Because of certain similar characteristics of their complementarity determining region 3 (CDR3), including preferential utilization of J_H6 elements and an extended length, it has been suggested that antigenic stimulation might be involved in leukaemogenesis. Utilizing single-cell PCR to amplify and sequence genomic DNA from individual normal human peripheral blood B cells, we have obtained 7/421 productively and 1/69 nonproductively rearranged V_H genes that used V_H1-69/DP-10. All productive rearrangements were unmutated, used J_H6 and had an average CDR3 length similar to that previously found in V_H1-69/DP-10-expressing CLL cells. These results suggest that CLL may arise from B cells commonly found in the peripheral B-cell repertoire and do not represent expansion of a unique subset of specific antigen-reactive B cells.