Impact on antibody responses of B-cell-restricted transgenic expression of a viral gene inhibiting activation of NF-κB and NFAT
In this work, we have assessed the impact in vivo of the evasion gene A238L of African swine fever virus, an inhibitor of both NF-κB- and NFAT-mediated transcription. The A238L gene was selectively expressed in mouse B lymphocytes using the promoter and enhancer sequences of the mouse Ig μ heavy chain. The IgM primary and IgG2b secondary serological responses and the number of splenic germinal centres in response to the TD antigens DNP-keyhole limpet hemocyanin and sheep red blood cells, respectively, were both lower in the transgenic mice, whereas the response to the TI type-1 and type-2 antigens DNP-Ficoll and DNP-LPS, respectively, were normal, except for the increased levels of IgG3 at day 14 in the DNP-LPS-immunized mice. Thus, it appears that neither p65 (NF-κB) nor NFAT is essential for B-cell development but, in a manner that is still unclear, may be relevant for their function.
KeywordsTransgenic Mouse Germinal Centre Serological Response African Swine Fever Virus Peanut Agglutinin
We acknowledge Moises Mallo for the production of the transgenic mice. We acknowledge Dr. Pedro Simas for providing us the pµs plasmid. SCP Almeida designed and performed the experiments, generated the transgenic mice colony, and wrote and revised the manuscript. VLO performed the experiments and revised the manuscript. RME Parkhouse designed the project and wrote and revised the manuscript. This work was supported by Fundação para a Ciência e Tecnologia, Ministério da Ciência e Ensino Superior (SFRH/BD/882/2000; POCTI/2000/MGI/36403) and by the Wellcome Trust (WT075813MA).
Conflict of interest
There are no conflicting interests. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
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