tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2023 Aug 9;2246599.
doi: 10.1080/22221751.2023.2246599. Online ahead of print. The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81
Qian Xie[SUP] 1 2 [/SUP], Xinzhong Liao[SUP] 1 2 [/SUP], Bi Huang[SUP] 1 2 [/SUP], Liangliang Wang[SUP] 1 2 [/SUP], Guancheng Liao[SUP] 1 2 [/SUP], Chuming Luo[SUP] 1 2 [/SUP], Simin Wen[SUP] 3 [/SUP], Shisong Fang[SUP] 4 [/SUP], Huanle Luo[SUP] 1 2 5 [/SUP], Yuelong Shu[SUP] 1 2 6 [/SUP]
Affiliations
A single-nucleotide polymorphism (SNP) rs12252-C of interferon-induced transmembrane protein 3 (IFITM3), resulting in a truncated IFITM3 protein lacking 21 N-terminus amino acids, is associated with severe influenza infection in the Chinese population. However, the effect of IFITM3 rs12252-C on influenza vaccination and the underlying mechanism is poorly understood. Here, we constructed a mouse model with a deletion of 21 amino acids at the N-terminus (NΔ21) of IFITM3 and then compared the antibody response between Quadrivalent influenza vaccine (QIV) immunized wild-type (WT) mice and NΔ21 mice. Significantly higher levels of HI titer, neutralizing antibodies (NAb), and immunoglobulin G (IgG) to H1N1, H3N2, B/Victory, and B/Yamagata viruses were observed in NΔ21 mice compared to WT mice. Correspondingly, the numbers of splenic germinal center (GC) B cells, plasma cells, memory B cells, QIV-specific IgG[SUP]+[/SUP] antibody-secreting cells (ASC), and T follicular helper cells (T[SUB]FH[/SUB]) in NΔ21 mice were higher compared with WT mice. Moreover, the 21-amino-acid deletion caused IFITM3 translocation from the endocytosis compartment to the periphery of cells, which also prevented the degradation of a co-stimulatory molecule of B cell receptor (BCR) CD81 on the cell surface. More importantly, a more interaction was observed between NΔ21 protein and CD81 compared to the interaction between IFITM3 and CD81. Overall, our study revealed a potential mechanism of NΔ21 protein enhancing humoral immune response by relocation to prevent the degradation of CD81, providing insight into SNP affecting influenza vaccination.
Keywords: IFITM3; IFITM3 rs12252; Vaccination; influenza virus.
. 2023 Aug 9;2246599.
doi: 10.1080/22221751.2023.2246599. Online ahead of print. The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81
Qian Xie[SUP] 1 2 [/SUP], Xinzhong Liao[SUP] 1 2 [/SUP], Bi Huang[SUP] 1 2 [/SUP], Liangliang Wang[SUP] 1 2 [/SUP], Guancheng Liao[SUP] 1 2 [/SUP], Chuming Luo[SUP] 1 2 [/SUP], Simin Wen[SUP] 3 [/SUP], Shisong Fang[SUP] 4 [/SUP], Huanle Luo[SUP] 1 2 5 [/SUP], Yuelong Shu[SUP] 1 2 6 [/SUP]
Affiliations
- PMID: 37556756
- DOI: 10.1080/22221751.2023.2246599
A single-nucleotide polymorphism (SNP) rs12252-C of interferon-induced transmembrane protein 3 (IFITM3), resulting in a truncated IFITM3 protein lacking 21 N-terminus amino acids, is associated with severe influenza infection in the Chinese population. However, the effect of IFITM3 rs12252-C on influenza vaccination and the underlying mechanism is poorly understood. Here, we constructed a mouse model with a deletion of 21 amino acids at the N-terminus (NΔ21) of IFITM3 and then compared the antibody response between Quadrivalent influenza vaccine (QIV) immunized wild-type (WT) mice and NΔ21 mice. Significantly higher levels of HI titer, neutralizing antibodies (NAb), and immunoglobulin G (IgG) to H1N1, H3N2, B/Victory, and B/Yamagata viruses were observed in NΔ21 mice compared to WT mice. Correspondingly, the numbers of splenic germinal center (GC) B cells, plasma cells, memory B cells, QIV-specific IgG[SUP]+[/SUP] antibody-secreting cells (ASC), and T follicular helper cells (T[SUB]FH[/SUB]) in NΔ21 mice were higher compared with WT mice. Moreover, the 21-amino-acid deletion caused IFITM3 translocation from the endocytosis compartment to the periphery of cells, which also prevented the degradation of a co-stimulatory molecule of B cell receptor (BCR) CD81 on the cell surface. More importantly, a more interaction was observed between NΔ21 protein and CD81 compared to the interaction between IFITM3 and CD81. Overall, our study revealed a potential mechanism of NΔ21 protein enhancing humoral immune response by relocation to prevent the degradation of CD81, providing insight into SNP affecting influenza vaccination.
Keywords: IFITM3; IFITM3 rs12252; Vaccination; influenza virus.