In vivo role of B lymphocytes in somatic transgene immunization.
Immunity generated by in vivo inoculation of plasmid DNA is a straightforward and potentially valuable new approach to immunization. Little is known about the type of cells involved, the various immunological aspects, and the destiny of the transgene. In this report, we describe a system in which immunity is the result of in vivo targeting of B lymphocytes. This was accomplished using plasmid DNA encoding an immunoglobulin heavy-chain gene under the control of immunoglobulin promoter and enhancer elements. We show persistence of the transgene in splenic B lymphocytes for at least 3 months, i.e., the average life span of long-lived B lymphocytes in the mouse. The transgene could not be detected in any other lymphoid or nonlymphoid organs over a period of 6 months. We also established that the transgene is integrated in the host DNA. These studies bring new understanding to the events underlying the in vivo use of plasmid DNA. Moreover, the characteristics of this new approach make somatic transgene immunization a model system to study the immunogenicity of endogenous antigens in adult animals.
Xiong
S
S
The Department of Medicine and Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0063, USA.
Gerloni
M
M
Zanetti
M
M
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D004742:Enhancer Elements, Genetic; D005260:Female; D018014:Gene Transfer Techniques; D005803:Genes, Immunoglobulin; D006801:Humans; D007114:Immunization / Q000379:methods*; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region