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Opsonophagocytic Killing Assay to Assess Immunological Responses Against Bacterial Pathogens
Published on: April 5, 2019
IL-7-dependent B lymphocytes are essential for the anti-polysaccharide response and protective immunity to
Anne K Shriner1, Hongqi Liu, Guizhi Sun
1Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Insights
Interleukin-7 (IL-7) signaling is crucial for young children's antibody responses to T cell-independent (TI) antigens like pneumococcal polysaccharide (PPS). Activating IL-7 pathways can restore these impaired immune responses in the young.
Area of Science:
- Immunology
- Pediatric immunology
- Vaccinology
Background:
- Young children exhibit impaired antibody responses to T cell-independent (TI) antigens, such as pneumococcal polysaccharide (PPS).
- B lymphopoiesis, the development of B cells, is IL-7 independent in early life but IL-7 dependent in adulthood.
- IL-7 signaling is hypothesized to be critical for effective antibody responses to TI antigens.
Purpose of the Study:
- To investigate the role of IL-7-driven B lymphopoiesis in promoting antibody responses to TI antigens in young versus adult mice.
- To determine if IL-7-dependent B cells are essential for immunity against TI antigens and bacterial challenge.
Main Methods:
- Comparison of immune responses to PPS vaccination and a model TI antigen (4-hydroxy-3-nitrophenyl-acetyl-Ficoll) in young and adult wild-type mice.
- Assessment of TI responses in young or adult mice deficient in IL-7 or IL-7Ralpha.
- Evaluation of TI responses in young IL-7 transgenic mice with enhanced IL-7 signaling.
- Testing resistance to Streptococcus pneumoniae challenge in various mouse models.
Main Results:
- Mice deficient in IL-7 or IL-7Ralpha showed severely impaired anti-PPS responses and did not survive S. pneumoniae challenge, indicating a requirement for IL-7-dependent B cells in TI immunity.
- Young IL-7 transgenic mice exhibited robust TI responses to PPS immunization, comparable to adult wild-type mice.
- Immunized young or adult IL-7 transgenic mice were completely resistant to S. pneumoniae challenge.
Conclusions:
- IL-7-dependent B cells are essential for mounting effective antibody responses to TI antigens and for protection against Streptococcus pneumoniae infection.
- Activating the IL-7 signaling pathway can restore impaired TI responses in young individuals.
- These findings highlight the potential of targeting IL-7 signaling to enhance pediatric immunity to TI antigens.
Abstract:
Young children are impaired in their response to T cell-independent (TI) Ags, such as pneumococcal polysaccharide (PPS). B lymphopoeisis early in life is IL-7 independent, whereas in adults it is IL-7 dependent. Therefore, we hypothesized that IL-7-driven B lymphopoiesis plays a critical role in promoting Ab responses to TI Ags. Young but not adult mice are impaired in responses to PPS vaccination and to 4-hydroxy-3-nitrophenyl-acetyl-Ficoll, a widely studied model TI Ag, and B1b cells generate Ab responses to these Ags. In this paper, we show that, despite having B1b, B1a, and MZ B cells-all of which are involved in TI responses-young wild-type or adult mice deficient either in IL-7 or in IL-7Ralpha are severely impaired in anti-PPS responses and do not survive Streptococcus pneumoniae challenge, indicating IL-7-dependent B cells are required for TI immunity. Consistent with this, PPS immunization induced a robust TI response in young IL-7 transgenic mice that was comparable to adult wild-type responses. Moreover, immunized young or adult IL-7 transgenic mice were completely resistant to S. pneumoniae challenge. Our data indicate that activating the IL-7 signaling pathway could restore impaired TI responses in the young.
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