期刊
FISH AND SHELLFISH IMMUNOLOGY REPORTS
卷 2, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.fsirep.2021.100038
关键词
CD40; CD154; IgZ; Costimulatory regulation; Antibacterial immunity
资金
- National Key Research and Development Program of China [2018YFD0900503, 2018YFD0900505]
- National Natural Science Foundation of China [31630083, 32173003]
The study found that Cd40-Cd154 interaction plays an important role in IgZ-mediated immunity, but is not essential for TI antigen-induced IgZ immune response. This suggests a differential role of Cd40-Cd154 interaction in bacterial TD and TI antigen-induced IgZ immunity.
CD40 and CD154 are one of the best-characterized costimulatory molecules essential for adaptive immunity, which extensively involved in T and B cell activation, IgM Ab production, isotype class switching, germinal center formation and affinity maturation. However, the functionality of CD40 and CD154 in IgZ-mediated immunity remains limited. In this study, we explored the regulatory role of Cd40-Cd154 interaction in IgZ-mediated antibacterial immunity in zebrafish. The results showed that the IgZ-mediated antibacterial response can be significantly induced in response to A. hydrophila infection. The percentage of Cd40(+)IgZ(+) B cells and the production of IgZ Ab were substantially increased upon A. hydrophila stimulation, but these reactions were markedly declined in Cd154 blockade fish by administering anti-Cd154 Ab or recombinant sCd40-Ig protein, accompanied with the impairment of the vaccine-initiated IgZ-mediated immunoprotection of fish against A. hydrophila infection. These observations suggested the essential role of Cd40-Cd154 interaction in IgZ-mediated bacterial immunity. Notably, the Cd40 and Cd154 costimulatory signals are required for a TD antigen-induced IgZ immunity, but are not indispensable for a TI antigen-induced IgZ immune response. These findings indicated the differential role of Cd40-Cd154 interaction in bacterial TD and TI antigen-induced IgZ immunity, which suggested the existence of diverse regulatory mechanisms underlying IgZ-mediated antibacterial immune reactions. To our knowledge, this is the first report to show the functional role of Cd40-Cd154 costimulatory signaling pathway in IgZ-mediated immune defense against bacterial infection. We hope this study will improve the current understanding of the coevolution between the IgZ/IgT immunoglobins and CD40/CD154 costimulatory molecules.
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