Mechanisms of chromosomal translocations in B cell lymphomas

Reciprocal chromosomal translocations involving the immunoglobulin (Ig) loc i are a hallmark of most mature B cell lymphomas and usually result in dysr egulated expression of oncogenes brought under the control of the Ig enhanc ers. Although the precise mechanisms involved in the development of these t ranslocations remains essentially unknown, a clear relationship has been es tablished with the mechanisms that lead to Ig gene remodeling, including V( D)J recombination, isotype switching and somatic hypermutation. The common denominator of these three processes in the formation of Ig-associated tran slocations is probably represented by the fact that each of these processes intrinsically generates double-strand DNA breaks. Since isotype switching and somatic hypermutation occur in germinal center (GC) B cells, the origin of a large number of B cell lymphomas from GC B cells is likely closely re lated to aberrant hypermutation and isotype switching activity in these B c ells.