LACK OF ALLELIC EXCLUSION IN B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA

We determined the immunoglobulin (Ig) V-H subgroup expressed by the le ukemia cells of 108 patients with B cell chronic lymphocytic leukemia (CLL). Surprisingly, we found that six samples (5%) each expressed Ig of more than one V-H subgroup. Southern blot analysis demonstrated tha t these samples each had rearrangements involving both Ig heavy chain alleles. Nucleic acid sequence analyses of the Ig cDNA revealed each t o express two functional Ig V-H genes: V(H)3-33 and V(H)4-39; V(H)3-7 and V(H)4-39; V(H)3-23 and V(H)4-61; V(H)2-70 and V(H)3-30.3; or V(H)3 -30 and V(H)4-b (DP67). One sample expressed three Ig V-H genes: V(H)2 -70, V(H)3-7, and V(H)4-59. Despite having more than one Ig heavy chai n transcript, each sample was found to express only one functional Ig light chain. From the primary sequence, sue deduced that the Ig of som e of these CLL samples should react with Lc1, a monoclonal antibody (m Ab) reactive with a supratypic cross-reactive idiotype present on Ig e ncoded by a subgroup of Ig V(H)4 genes (namely, V(H)4-39, V(H)4-b [DP- 67], V(H)4-59, or V(H)4-61), and B6, an mAb that reacts with Ig encode d by certain Ig V(H)3 genes (namely, V(H)3-23, V(H)3-30, or V(H)3-30.3 ), and/or modified staphylococcal protein A (SpA), a 45-kilodalton bac terial ''superantigen'' that reacts with most Ig of the V(H)3 subgroup . Flow cytometric analyses revealed that such samples did in fact reac t with Lc1 and B6 and/or SpA, but not with control mAbs of irrelevant specificity. This study demonstrates that a subset of CLL patients hav e leukemic B cells that express more than one functional Ig heavy chai n.