Widespread B cell perturbations in HIV-1 infection afflict naive and marginal zone B cells

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• B cell perturbations are characteristic of HIV-1 infection.
• Exhausted CD21-negative memory B cells increase due to persistent activation.
• This exhaustion impacts B cells beyond memory populations.

Purpose of the Study:

• To investigate B cell exhaustion in antigen-inexperienced naive and marginal zone (MZ) B cells during HIV-1 infection.
• To characterize the phenotype and function of exhausted naive and MZ B cells.
• To assess the impact of antiretroviral therapy on these B cell populations.

Main Methods:

• High-dimensional flow cytometry was employed.
• Analysis focused on peripheral blood B cell subsets.
• B cell receptor (BCR)-dependent stimulation assays were performed.

Main Results:

• Exhausted CD21-negative phenotype is present in naive and MZ B cells during acute and chronic HIV-1.
• These cells show reduced CD21 levels and impaired BCR signaling.
• Naive and MZ B cells exhibit distinct chemokine receptor and activation marker expression compared to CD21-positive cells.
• Antiretroviral treatment effectively normalized these peripheral B cell populations.

Conclusions:

• HIV-1 infection causes broader B cell impairment, affecting antigen-inexperienced cells.
• Exhausted naive B cells may hinder the development of new B cell responses.
• Monitoring naive B cell function is crucial in managing HIV-1 infection.