REARRANGEMENT, HYPERMUTATION, AND POSSIBLE PREFERENTIAL USE OF A V(H)5 GENE, V(H)32, IN A HODGKINS CELL-LINE

Nonrandom use of immunoglobulin variable (V) gene segments is a featur e of some B-cell neoplasms, possibly as a consequence of antigen selec tion. In Hodgkin's disease, the primary tissues, cell lines, and even single Reed-Sternberg cells can carry immunoglobulin gene rearrangemen ts. Here, we examined the immunoglobulin heavy-chain genes of a well-c haracterized Hodgkin's-derived cell line, L428, and found a hypermutat ed V(H)32 gene involving a conventional V(N)D(N)J4-C gamma 4 rearrange ment. V(H)32 is one of two rearranging members of the V(H)5 family tha t is also rearranged preferentially in some B-cell neoplasms and famil ial CLL. Unexpectedly, the closest known rearranged sequence match for the rearranged V-H gene of L428 was found in the single Reed-Sternber g cells of lymphocyte-predominance Hodgkin's disease, and is a mutated V(H)251, the only other rearranging member of the V(H)5 family. Assum ing random usage of the human V-H pool, the chance of coincident V(H)5 family gene rearrangement in the two cases of Hodgkin's disease is on ly about 10(-3). Biased use of V-H genes suggests a B-cell target that is either selected by antigen or vulnerable to transformation at an e arly antigen-independent, developmental stage. These findings raise th e question whether similar processes operate in Hodgkin's disease.