Lymphomas with follicular and monocytoid B-cell components - Evidence for a common clonal origin from follicle center cells

We investigated the clonal relationship between follicular center cell and monocytoid B-cell components of non-Hodgkin lymphoma by isolating the compo nents and comparing the nucleotide sequences of the complementarity-determi ning region (CDR)3 of the rearranged immunoglobulin heavy chain (IgH) gene. Paraffin blocks from 4 cases with amplifiable DNA using the polymerase cha in reaction (PCR) were identified. Multiple representative cell clusters of the 2 components were obtained by microdissection, and the IgH CDR3 was am plified using a seminested PCR. Most of the PCR products obtained from both tumor components in each case had identical lengths when analyzed with pol yacrylamide gel electrophoresis (PAGE) and identical migratory patterns on denaturing gradient gel electrophoresis (DGGE). These findings indicate seq uence identity of the IgH CDR3 of both tumor components. Sequence analysis showed that point mutations were responsible for bands from the same case t hat had nonidentical migratory patterns by DGGE. The components in each of the 4 cases studied have the same clonal origin. Intraclonal sequence varia tions in the IgH gene were observed in 2 cases, consistent with the presenc e of continued somatic hypermutation after establishment of the clone. The expression of CD10 and bcl-2, as well as the detection of bcl-2 rearrangeme nts in 2 cases, indicate that these lymphomas are of follicular center cell origin.