Immunoglobulin VH4 gene usage in B lymphoid leukaemias

Abstract

VH4 gene rearrangements occur in a similar proportion of cases of B lineage acute lymphoblastic leukaemia (ALL) and B chronic lymphocytic leukaemia (B CLL). However, there may be differences in the pattern of VH4 gene usage between these disorders as is the case for VH1 gene rearrangements. To examine this, we analysed the sequences of 24 PCR-amplified clonal VH4 gene rearrangements from a series of 15 cases of ALL and nine cases of CLL. Five distinct groups of genes were rearranged, three of which (represented by V2-1, V71-2/V71-4, V4.21) have been described in rearranged form in normal B lymphoid tissues. The most frequently rearranged gene was V4.21 which is strongly associated with autoimmune reactivity. V71-2, V71-4 and V2-1 were more frequently rearranged in CLL than ALL. The remaining two groups (represented by V4.33, V4.35) have not previously been described in rearranged form. One of these, V4.35, was seen only in ALL rearrangements. Both V4.35 and a VH1 gene, 20P3, which is also preferentially rearranged in ALL, are located at the 3' end of the VH locus. The location of these genes suggests that their rearrangement may be developmentally regulated in ALL. The findings in this study confirm restricted repertoires of IgH gene rearrangement in ALL and CLL. Characterization of IgH repertoires provides a means of correlating these transformed B cell populations with normal B cell developmental compartments. Moreover, the distinctive repertoires in ALL and CLL may reflect important differences in the ontogenic timing and microenvironmental milieu of tumourigenesis in these disorders.