ONGOING IMMUNOGLOBULIN GENE-MUTATIONS IN MANTLE CELL LYMPHOMAS

Mantle cell lymphomas (MCL) frequently show a vaguely follicular growt h pattern. This phenomenon is thought to result from the colonization of reactive B-cell follicles by tumour cells. In view of the unique pr operty of the germinal centre environment, antigen stimulation may pla y a role in the expansion of the tumour. To assess this, we have exami ned ongoing Ig mutations, which are genetic markers of B cells in pers istent response to antigen stimulation, in five MCLs including two cas es derived from the gastrointestinal tract known as lymphomatous polyp osis (LP). We have specifically analysed Ig ongoing mutations in tumou r cells from multiple lesions in one case and in tumour cells microdis sected from colonized follicles in two cases. The consensus Ig V-H seq uences in four MCLs were identical, or almost identical (three cases 1 00%, one case 99% homology) to the published germlines, which in each case were those frequently employed by autoantibodies. The consensus I g V-H sequence in the remaining case displayed 95 . 5% homology to the closest published germline. This may represent derivation from an unk nown V-H germline or a rare instance of somatic mutations. Extensive s equencing of the rearranged Ig genes revealed ongoing mutations within the tumour clone in two cases: one was a LP with multiple lesions of the gastrointestinal tract and the other was a nodal MCL in which tumo ur cells from colonized follicles were analysed, Our results indicate that MCLs are derived from pre-germinal centre B cells, possibly autor eactive B-cell clones. The ongoing mutations identified suggest a poss ible involvement of antigen stimulation in the clonal expansion of a p roportion of MCLs.