AbstractThe functional immunoglobulin (Ig) genes of B lymphocytes undergo somatic mutations during immune responses. These mutations modify the antigen binding site of the immunoglobulins, thereby enhancing the average affinity of the antibodies produced. The molecular mechanism underlying these B cell hypermutations remains unresolved, partly because it is difficult to grow normal B cells in long‐term cell cultures and because there is no suitable transformed or malignant B cell line which generates mutations in its immunoglobulin genesin vitro. Here, we show that the recently established follicular lymphoma line HF‐1.3.4 generates somatic hypermutationsin vitroat a high frequency of 0.7 × 10−6mutations per base pair per generation in standard cell cultures (RPMI 1640 + 5 fetal calf serum). This shows for the first time that B cell hypermutation can occur without T cells or T cell factors. The mutation frequency increased approximately tenfold to 1 × 10−5mutations/base pair/generation with B cell‐specific growth factors (interleukins −2 and −4 and three antibodies stimulatory to HF‐1.3.4 cells). This HF‐1.3.4 lymphoma line may help to elucidate the molecular mechanism of Ig
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