Excess BAFF May Impact HIV-1-Specific Antibodies and May Promote Polyclonal Responses Including Those from First-Line...

Area of Science:

• Immunology
• Virology
• B-cell Biology

Background:

• Blood B-cell Activating Factor (BAFF) levels increase with HIV-1 disease progression.
• Excess BAFF is linked to B-cell deregulation, including increased marginal zone precursor-like (MZp) cells.
• MZp cells in HIV-1 progressors show signs of exhaustion and an interferon signature similar to autoimmune diseases.

Purpose of the Study:

• To investigate the role of excess BAFF in HIV-1 infection.
• To determine if excess BAFF affects HIV-1-specific IgG responses.
• To explore the impact of BAFF on B-cell polyreactivity and autoreactivity.

Main Methods:

• Analysis of BAFF levels and B-cell populations in HIV-1 infected individuals.
• In vitro experiments assessing BAFF's effect on B-cell antibody production.
• RNA sequencing (RNASeq) of blood MZp cells.

Main Results:

• HIV-1-specific IgG quantity correlates with disease progression.
• In vitro, excess BAFF stimulates polyclonal IgM and IgG production, including from MZp cells.
• MZp cells from progressors exhibit a propensity for Ig production, utilizing IGHV genes linked to broadly neutralizing antibodies and autoantibodies.

Conclusions:

• Excess BAFF in HIV-1 infection may impair HIV-1-specific antibody generation.
• BAFF contributes to polyclonal B-cell activation and potentially autoreactivity.
• The role of MZp cells and their associated IGHV gene usage in HIV-1 pathogenesis requires further investigation.