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Complement receptors CD21/35 link innate and protective immunity during Streptococcus pneumoniae infection by
Karen M Haas1, Minoru Hasegawa, Douglas A Steeber
1Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Abstract:
The CD21/35 receptor provides an important link between innate and adaptive immunity. Its importance during protective immune responses to encapsulated extracellular bacteria was assessed using a new line of mice completely deficient in CD21/35 expression (CD21/35(-/-)). CD21/35 expression was essential for the rapid trapping of C3dg-antigen complexes by B cells in vivo, especially in splenic marginal zones. Despite normal B cell development in CD21/35(-/-) mice, T cell-independent and -dependent antibody responses to low-dose antigens were significantly decreased, with a striking impairment in IgG3 responses. Accordingly, CD21/35(-/-) mice were more susceptible to acute lethal Streptococcus pneumoniae infection. Thus, CD21/35 expression is critical for early protective antibody responses to lethal pathogens that rapidly multiply and quickly overwhelm the immune system.
Insights
The CD21/35 receptor is crucial for effective immune responses against bacterial infections. Mice lacking CD21/35 showed impaired antibody production and increased susceptibility to lethal pathogens like Streptococcus pneumoniae.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- The CD21/35 receptor acts as a bridge between innate and adaptive immunity.
- Understanding its role is vital for developing strategies against encapsulated extracellular bacteria.
Purpose of the Study:
- To investigate the critical role of CD21/35 receptor expression in protective immunity against bacterial pathogens.
- To assess the impact of CD21/35 deficiency on B cell function and antibody responses in vivo.
Main Methods:
- Utilized a novel mouse model completely deficient in CD21/35 expression (CD21/35(-/-)).
- Evaluated the in vivo trapping of C3dg-antigen complexes by B cells, particularly in splenic marginal zones.
- Assessed T cell-independent and -dependent antibody responses to low-dose antigens and susceptibility to Streptococcus pneumoniae infection.
Main Results:
- CD21/35 expression was essential for efficient C3dg-antigen complex trapping by B cells.
- CD21/35(-/-) mice exhibited significantly decreased T cell-independent and -dependent antibody responses, with impaired IgG3 production.
- CD21/35(-/-) mice showed increased susceptibility to lethal Streptococcus pneumoniae infection.
Conclusions:
- CD21/35 receptor expression is critical for initiating early protective antibody responses.
- This receptor plays a vital role in combating rapidly multiplying pathogens that can overwhelm the immune system.
- Targeting CD21/35 may offer therapeutic potential for enhancing immunity against severe bacterial infections.