B-lymphocyte dysfunction in chronic HIV-1 infection does not prevent cross-clade neutralization breadth

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Aberrant expression of regulatory receptors like programmed death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) is known to cause T cell exhaustion in chronic HIV-1 infection.
• The impact of these regulatory receptors on B-lymphocyte function during HIV-1 infection is less understood.
• Disruption of the peripheral B cell compartment may lead to reduced neutralizing antibody activity.

Purpose of the Study:

• To investigate the expression of PD-1 and BTLA in B cells from HIV-1-infected individuals.
• To assess the relationship between B cell dysregulation markers, immune activation, and CD4 T cell counts.
• To evaluate immunoglobulin production and neutralizing antibody activity in the context of B cell dysfunction during HIV-1 infection.

Main Methods:

• Flow cytometry was used to evaluate B cell expression of PD-1, BTLA, CD95, and Ki-67.
• Analysis included B cells from HIV-1-viremic, aviremic, and healthy subjects.
• Viral load, immunoglobulin levels, CD4 T cell counts, and plasma cross-clade neutralizing activity were assessed.

Main Results:

• Viremic HIV-1 subjects exhibited B cell dysregulation, characterized by disrupted peripheral B cell subsets, increased PD-1, and decreased BTLA expression compared to controls.
• PD-1 and BTLA expression showed divergent correlations with immune activation, CD4 T cell counts, and total plasma IgG levels.
• In viremic subjects, total IgG levels positively correlated with cross-clade neutralizing antibody activity.

Conclusions:

• HIV-1 infection leads to significant B lymphocyte dysregulation, indicated by altered expression of PD-1 and BTLA.
• Despite B cell dysfunction, functional cross-clade neutralizing antibodies persist in the plasma of chronically infected individuals.
• These findings highlight the complex interplay between viral load, B cell regulation, and humoral immunity in HIV-1 infection.