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Hodgkin’s disease (HD) is a lymphoid neoplasmcharacterized by a low frequency of malignant gianttumor cells, known as Hodgkin’s and Reed-Sternberg(HRS) cells. Sequence analysis of the immunoglobulinheavy chain hypervariable region (IgH V) genes ofHRS cells revealed multiple nucleotide substitutions,indicating somatic mutations, and suggested that HRScells originate from germinal center B cells or theirprogeny. We previously reported that CD99-antisensetransfected B cell lines led to the generation of cellswith a HRS phenotype. Because it is considered thatHRS cells in HD carry somatic mutations of the IgHgenes, we assume that somatic mutation may takeplace in the IgH genes of HRS-like cells which do notexpress CD99. Here we report that CD99 downregulatedBJAB cell line has several mutations in IgH Vgenes. The frequency of mutation was 5.2 × 10−4mut.bp−1 out of total sequenced cell clones. On thecontrary, control vector transfected BJAB cell line orCD99 downregulated IM9 cell line did not show anymutations on single strand conformationalpolymorphism (SSCP) and sequence analysis. Weexpect that the analysis of the mutation pattern of theCD99-deficient BJAB cell line might be the basis forthe understanding of the molecular and cellularmechanism that regulate somatic mutation and B cells election.