Impairment of B-cell functions during HIV-1 infection

Abstract

A variety of B-cell dysfunctions are manifested during HIV-1 infection, as reported early during the HIV-1 epidemic. It is not unusual that the pathogenic mechanisms presented to elucidate impairment of B-cell responses during HIV-1 infection focus on the impact of reduced T-cell numbers and functions, and lack of germinal center formation in lymphoid tissues. To our understanding, however, perturbation of B-cell phenotype and function during HIV-1 infection may begin at several different B-cell developmental stages. These impairments can be mediated by intrinsic B-cell defects as well as by the lack of proper T-cell help. In this review, we will highlight some of the pathways and molecular interactions leading to B-cell impairment prior to germinal center formation and B-cell activation mediated through the B-cell receptor in response to HIV-1 antigens. Recent studies indicate a regulatory role for B cells on T-cell biology and immune responses. We will discuss some of these novel findings and how these regulatory mechanisms could potentially be affected by the intrinsic defects of B cells taking place during HIV-1 infection.

Preservation of Peripheral T Follicular Helper Cell Function in HIV Controllers

“…The dysregulation of the B cell compartment in HIV infection is likely caused by both direct immune stimulation and bystander mechanisms of immunologic damage (14); some of which persist in the presence of ART (15). A recent study reported that bulk, non-antigen-specific RM B cells in peripheral blood are depleted during HIV infection, while AM and TLM cell frequencies expand.…”

“…As Tfh cell expansion has been associated with a concurrent expansion of B cells and plasma cells in lymphoid germinal centers, we next studied bulk and HIV-specific B cell phenotypes in the peripheral blood of the cohorts to determine how the observed To analyze the effects of antigenemia on memory B cell subsets, bulk B cells were separated into the four following memory subsets based on expression of CD21 and CD27 as previously described (14,15,17): CD27 ϩ CD21 Ϫ activated memory (AM), CD27 ϩ CD21 ϩ resting memory (RM), CD27 Ϫ CD21 Ϫ tissue-like memory (TLM), and CD27 Ϫ CD21 ϩ intermediate memory (IM). We found that peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals have altered profiles of B cell memory subtypes compared to those from uninfected individuals.…”

“…Similarly, memory B cells have been demonstrated to be phenotypically skewed during chronic HIV infection by direct and bystander activation mechanisms (14,15). This perturbation is typified by an increased relative fraction of activated memory cells, plasmablasts, and exhausted B cells and a reduction in long-lived plasma cells.…”

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

“…Although HIV does not productively infect B cells, numerous phenotypic and functional abnormalities of B cells have been described in HIV disease (21,22). The indirect and persistent effects of ongoing HIV replication have been associated with aberrant B cell activation, increased B cell exhaustion, as well as deficiencies in the development of normal B cell memory (21).…”

“…The indirect and persistent effects of ongoing HIV replication have been associated with aberrant B cell activation, increased B cell exhaustion, as well as deficiencies in the development of normal B cell memory (21). Whereas resting memory B cells represent the predominant memory subset in healthy individuals, their frequencies are reduced in almost all stages of HIV disease, regardless of treatment status (21,22). In untreated HIV-viremic individuals, tissue-like and activated memory B cells are the predominant memory subsets, the former being associated with HIV-induced cellular exhaustion and the latter, apoptosis (21).…”