Absence of immunoglobulin variable region hypermutation in a large cell lymphoma after in vivo and in vitro propagation

Abstract

Abstract Several genetic mechanisms have been shown to diversity the expressed antibody repertoire of committed B lymphocytes. These include somatic hypermutation, V gene replacement, and ongoing gene rearrangement. These mechanisms may be operational at discrete points in the B-cell differentiation pathway and may generate idiotypic diversity in various malignant B-cell tumors. Hypermutation of the Ig variable region has been shown to occur in follicular lymphoma, but not in pre-B cell acute lymphoblastic leukemia, Burkitt's lymphoma, chronic lymphocytic leukemia, or myeloma. To study hypermutation in a large cell lymphoma, we use a polymerase chain reaction-based approach, employing consensus VH and JH primers, to clone and sequence rearranged Ig heavy chain variable regions. Neither tumor cells immortalized in rescue fusions nor idiotypic variants of a tumor-derived cell line generated through ongoing lambda light chain gene rearrangements show any significant number of variable region mutations. Thus, at the in vivo stage of B- cell differentiation from which this large cell lymphoma arose, Ig variable region hypermutation was not occurring, nor did it occur during propagation in vitro of these tumor cells. Thus, the window of hypermutation in malignant B-cell tumors is more precisely defined, which may have clinical implications for diagnostic and therapeutic approaches directed at the Ig variable region.