Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• B cell dysfunction is evident in HIV disease, but the origin of rare HIV-specific antibodies remains unclear.
• Understanding B cell responses is crucial for developing effective HIV therapies and vaccines.

Purpose of the Study:

• To investigate HIV-specific B cell responses in individuals with HIV infection.
• To identify the B cell subsets responsible for generating HIV-specific antibodies.

Main Methods:

• Used HIV envelope gp140 and mutant probes to analyze peripheral blood B cells from HIV-infected individuals.
• Evaluated HIV-specific responses across different B cell subsets, including activated, exhausted, and resting memory B cells.
• Corroborated findings with transcriptional analyses.

Main Results:

• HIV-specific responses were enriched in abnormal B cell subsets (activated and exhausted memory cells) in infected individuals.
• Responses targeting the coreceptor binding site emerged early, while those targeting the CD4 binding site were delayed.
• Resting memory B cells showed HIV-specific responses in individuals with controlled viremia.

Conclusions:

• HIV infection skews B cell responses towards abnormal subsets, potentially impairing antibody effectiveness.
• Memory B cell abnormalities are implicated in the ineffectiveness of the antibody response during HIV infection.