Dengue virus-specific memory B cell subsets differ as a function of infection history

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Dengue virus (DENV) serotypes 1-4 pose a significant global health risk.
• DENV infection induces protective immunity, with memory B cells (MBCs) potentially conferring long-lasting protection.
• The development of DENV-specific MBCs following multiple DENV infections is not well understood.

Purpose of the Study:

• To comprehensively evaluate the frequencies of DENV-specific B cell subsets in individuals with primary (1°) versus secondary (2°) DENV infection history.
• To assess the temporal dynamics of DENV-specific MBCs from acute infection up to 18 months post-symptom onset.
• To determine if secondary DENV immunity results in quantitative or qualitative changes in the memory B cell pool.

Main Methods:

• Analysis of 58 samples from dengue cases with varying infection histories (primary vs. secondary).
• Comprehensive evaluation of nine distinct DENV-specific B cell subsets.
• Longitudinal sampling to track MBC dynamics over 18 months post-symptom onset.

Main Results:

• DENV-specific B cell frequencies differed significantly at the subset level between primary and secondary infections, despite similar total frequencies.
• Durable DENV-specific MBC subsets (IgG+, IgM+, atypical, class-switched IgD-) accumulated with multiple exposures.
• Certain DENV-specific MBC subsets peaked later (>3 months post-symptom onset) in secondary immunity, indicating ongoing maturation.

Conclusions:

• DENV-specific MBC subsets are distinct based on infection history, suggesting a qualitative reprogramming of the memory pool rather than a simple quantitative boost.
• The accumulation and delayed maturation of specific MBC subsets in secondary DENV immunity may contribute to enhanced protective responses.
• Findings highlight the complex immunological memory generated by sequential DENV infections.