Insights into B cells and HIV‐specific B‐cell responses in HIV‐infected individuals

Abstract

Human immunodeficiency virus (HIV) disease is associated with dysregulation and dysfunction involving all major lymphocyte populations, including B cells. Such perturbations occur early in the course of infection and are driven in large part by immune activation resulting from ongoing HIV replication leading to bystander effects on B cells. While most of the knowledge regarding immune cell abnormalities in HIV-infected individuals has been gained from studies conducted on the peripheral blood, it is clear that the virus is most active and most damaging in lymphoid tissues. Here, we discuss B-cell perturbations in HIV-infected individuals, focusing on the skewing of B-cell subsets that circulate in the peripheral blood and their counterparts that reside in lymphoid tissues. This review also highlights recent advances in evaluating HIV-specific B-cell responses both in the memory B-cell compartment, as well as in circulating antibody-secreting plasmablasts and the more differentiated plasma cells residing in tissues. Finally, we consider how knowledge gained by investigating B cells in HIV-infected individuals may help inform the development of an effective antibody-based HIV vaccine.

Post-treatment control of HIV infection

“…CD4 + and CD8 + T cells, as well as NK cells, have significant noncytolytic functions that have not been included in our model. Our model also did not consider HIV-specific antibody responses (63,64) that could affect the details of the viral dynamic model in a number of ways (65). Whether these features of immune responses play a role in PTC is unknown.…”

Preservation of Peripheral T Follicular Helper Cell Function in HIV Controllers

“…Antigen-experienced B cells expressing CD27 can be differentiated into several distinct phenotypic and functional subsets based on lineage and differentiation markers, and the prevalence of these subpopulations is profoundly skewed in HIV infection (14,18). 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).…”

“…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.…”