Multifaceted B cell response to transient HIV viremia in elite controllers

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Chronic HIV infection causes B cell dysfunction, characterized by increased tissue-like memory (TLM) and activated memory B cells (MBCs), alongside a decrease in resting MBCs.
• TLMs exhibit inhibitory receptor expression and poor responses to soluble antigens, but their origins and expansion mechanisms in HIV remain poorly understood.

Purpose of the Study:

• To investigate the origin and expansion mechanisms of TLM B cells in chronic HIV infection.
• To characterize the B cell response, including TLM heterogeneity, during transient HIV viremia in an elite controller.

Main Methods:

• Bulk heavy chain BCR sequencing of MBC subsets from individuals with treated HIV.
• Multi-omics analysis, including single-cell RNA/BCR sequencing, of peripheral blood mononuclear cells (PBMCs) during transient HIV viremia.
• Analysis of B cell subset phenotypes, mutation levels, and diversity.

Main Results:

• TLMs showed reduced mutation and diversity compared to other MBCs, suggesting an innate-like or less mature B cell origin.
• Transient HIV viremia induced a functional increase in Env-reactive IgG and non-TLM MBCs.
• Single-cell analysis revealed coordinated TNF-α, IFN-α, and IFN-γ responses across B cell subsets.

Conclusions:

• The study provides novel insights into the heterogeneous nature of TLMs and their functional responses during HIV infection.
• B cell responses to transient HIV viremia involve coordinated cytokine signaling and expansion of specific MBC subsets.