OBJECTIVE: To explore the feasibility of construction of the universal nucleic acid vaccine against B-cell lymphoma. METHODS: RT-PCR was employed to obtain the immuncy losulin heavy chain variable region (IgHV1) gene fragments of the Namalwa cell, normal fetal umbilical cord blood and adult peripheral blood. Then these RT-PCR products were cloned into the eukaryotic expression vector pcDNA3.0 and sequenced. Six plasmids that had high identities with the germ line genes were mixed to serve as vaccines. Eighteen Balb/c mice were divided randomly into three groups and were immunized respectively with the six mixed plasmids, the specific IgHV1 fragment of the Namalwa cell and the blank plasmid pcDNA3.0. 100 microg plasmid and 5 microg hIL-6 per mouse were injected into the muscle, 3 times in 4 weeks. Western blotting and indirect immunofluorescence staining were used to assess the humoral immune responses against the Namalwa cell. RESULTS: The specific humoral immune responses against the Namalwa lymphoma cell could be induced in both the IgHV1-mix group and the Na-IgHV1 group, and the antibodies could recognize the nature antigenic determinants in the surface of the Namalwa cell. The antibodies could be detected since the fourth week after the first immunization, and reached the climax at the sixth week. There was no significant difference of the titers of the antibodies between the two groups. The antibody couldn't be found in the negative control group. CONCLUSION: The mixed IgHV plasmids can be used as the universal nucleic acid vaccine against the B-cell lymphoma which expresses the same IgHV1 family genes.