Influence of dendritic cells on B-cell responses during HIV infection

Abstract

Dendritic cells (DCs) modulate B-cell differentiation, activation, and survival mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF). DC populations have been reported to be affected in number, phenotype and function during HIV infection and such alterations may contribute to the dysregulation of the B-cell compartment. Herein, we reflect on the potential impact of DC on the pathogenesis of HIV-related B cell disorders, and how DC status may modulate the outcome of mucosal B cell responses against HIV, which are pivotal to the control of disease. A concept that could be extrapolated to the overall outcome of HIV disease, whereby control versus progression may reside in the host's capacity to maintain DC homeostasis at mucosal sites, where DC populations present an inherent capacity of modulating the balance between tolerance and protection, and are amongst the earliest cell types to be exposed to the virus.

Figure 1

The implication of BLyS/BAFF expression status in the modulation of HIV-specific reponses. Control of HIV infection is reflected by the capacity to regulate BLyS/BAFF expression status at mucosal sites, where the main battle against HIV takes place, promoting efficient HIV-specific B- and T-cell responses, viewed to block systemic invasion by the virus. In contrast, breaching of systemic integrity and progression of HIV infection is reflected by the incapacity to control BLyS/BAFF levels at mucosal sites, leading to dysregulated B- and T-cell responses, impairing the generation of highly protective HIV-specific immunity.