SOMATIC HYPERMUTATIONS IN THE IMMUNOGLOBULIN GENES OF 2 NEW HUMAN LYMPHOMA LINES OF LYMPHATIC FOLLICLE ORIGIN

Variable immunoglobulin heavy-chain regions (VDJ) of two newly established human lymphoma cell lines (HF-1 and HF-4) were sequenced. The most homologous germline V-H gene found for both the HF-1 and HF-4 sequences was V(H)26 of the V(H)3a (V gene) family (82% and 91% homologies, respectively). The J(H) region of the HF-4 heavy-chain sequence contained two nucleotide differences compared to the published germline J(H)3 gene. The D(H)J(H) region of the HF-1 gene had a record high number (20%) of somatic mutations. The numerous hypermutations found in the HF-1 cell line support the hypothesis that in some human follicular lymphomas, mutations continue to accumulate in immunoglobulin genes during the malignant growth. Follicular lymphoma cell lines, which have an active mutational machinery, in future may help to solve the molecular events behind the somatic hypermutations modifying immunoglobulin genes of B lymphocytes.