Primary mediastinal
B-cell lymphoma (PMBL) is a subentity of
diffuse large B-cell lymphoma with characteristic clinical, histomorphologic, immunophenotypical, and genetic features. Unlike other
B-cell lymphomas, PMBL has not yet been the subject of comprehensive molecular studies on the rearranged
immunoglobulin (Ig) gene. Such investigations have proved essential to obtaining information about the differentiation stage of the lymphomagenic B cell. In the present study, the clonally rearranged
immunoglobulin heavy-chain gene of 13 PMBL cases is analyzed by polymerase chain reaction (PCR) in conjunction with cloning and
DNA sequencing. Twelve of 13 rearrangements were potentially functional. All clonally rearranged immunoglobulin genes bore a high load of somatic mutations (average, 13.0%), which appeared to be selected for a functional antibody in the majority of cases. The comparison of cloned PCR products revealed no evidence of ongoing mutation of the
immunoglobulin variable gene. By means of
reverse-transcriptase PCR,
lymphoma-specific
immunoglobulin transcripts were detected in 8 of 13 cases, all of which were of the postswitched type, whereas
immunoglobulin protein expression was undetectable except for 1 case. A PMBL cell line, MedB-1, generated from an
IgG(-) parental
tumor, constitutively expressed
IgG protein in a subset of cells, which was moderately suppressed by
interleukin-4 and up-regulated in the presence of
dexamethasone. PMBL is thus characterized by a heavily mutated, class-switched immunoglobulin gene without evidence of ongoing mutational activity. Moreover, our data indirectly suggest that regulation by extrinsic signals contributes to the
immunoglobulin-negative phenotype of PMBL.