Maintenance of HIV-Specific Memory B-Cell Responses in Elite Controllers Despite Low Viral Burdens

Abstract

Human immunodeficiency virus (HIV)-specific B-cell responses in infected individuals are maintained by active HIV replication. Suppression of viremia by antiretroviral therapy (ART) leads to quantitative and qualitative changes that remain unclear. Accordingly, B-cell responses were investigated in elite controllers (ECs), who maintain undetectable HIV levels without ART, and in individuals whose viremia was suppressed by ART. Despite a higher HIV burden in the ART group, compared with the EC group, frequencies of HIV-specific B cells were higher in the EC group, compared with those in the ART group. However, the initiation of ART in several ECs was associated with reduced frequencies of HIV-specific B cells, suggesting that responses are at least in part sustained by HIV replication. Furthermore, B-cell responses to tetanus toxin but not influenza hemagglutinin in the ART group were lower than those in the EC group. Thus, the superior HIV-specific humoral response in ECs versus ART-treated individuals is likely due to a more intact humoral immune response in ECs and/or distinct responses to residual HIV replication.

B‐cell responses to HIV infection

“…Furthermore, we demonstrated that while both cohorts of HIV-infected individuals had an HIV-specific response that was enriched within their resting memory B cells, frequencies were significantly higher in the elite controllers, despite a lower cellular HIV burden than in the ART group (161). These findings confirm those of a previous study (162), and extend observations that an intact humoral immune capacity may be responsible for a superior HIV-specific B-cell response.…”

“…With regard to the populations of memory B cells that circulate in the peripheral blood of elite controllers, we recently demonstrated that they more closely resemble those of healthy donors than those of HIV-infected individuals whose viremia is suppressed by ART (161). Furthermore, we demonstrated that while both cohorts of HIV-infected individuals had an HIV-specific response that was enriched within their resting memory B cells, frequencies were significantly higher in the elite controllers, despite a lower cellular HIV burden than in the ART group (161).…”

Impact of BAFF Blockade on Inflammation, Germinal Center Reaction and Effector B-Cells During Acute SIV Infection

“…In particular, increased proportions of atypical (CD21 lo ) memory B-cells and loss in conventional, Resting Memory (RM, CD21 + CD27 + ) Bcells are hallmark features of chronic infection by HIV or Simian Immunodeficiency virus (SIV) (8). Among atypical memory Bcells, two subsets have been characterized: Tissue-like memory B-cells (TLM, CD21 lo CD27 lo ) enriched in Envelope-specific Bcells (9,10) and Activated Memory B-cells (AM, CD21 lo CD27 + ). Rapid loss in AM B-cells at the acute phase of infection predicts accelerated progression toward the chronic phase (11).…”

“…During chronic infection, TLM B-cells produce poly-reactive IgG, part of them being protective/neutralizing Abs. Functional HIV-specific memory Bcells are associated with efficient viral neutralization in Elite controllers (10,15), and significant recovery of HIV-specific RM B-cells requires initiation of anti-retroviral therapy as soon as the acute phase of infection (16).…”

Contamination with HIV antibody may be responsible for false positive results in specimens tested on automated platforms running HIV 4th generation assays in a region of high HIV prevalence

“…It is possible that there were additional true HIV infections amongst the inconclusive samples: virus replication is responsible for boosting antibody and levels can decline in elite controllers and patients on prolonged ART. [ 14 ], [ 15 ],[ 16 ] Such patients might have undetectable viral loads and low HIV antibody. However, this is rare and unlikely to account for the large number of weakly positive results we encountered.…”