Marginal Zone B-Cell Populations and Their Regulatory Potential in the Context of HIV and Other Chronic Inflammatory Conditions

Abstract

Inflammation in the context of Human Immunodeficiency Virus (HIV) establishes early and persists beyond antiretroviral therapy (ART). As such, we have shown excess B-cell activating factor (BAFF) in the blood of HIV-infected progressors, as soon as in the acute phase, and despite successful ART. Excess BAFF was associated with deregulation of the B-cell compartment; notably, with increased frequencies of a population sharing features of both transitional immature (TI) and marginal zone (MZ) B-cells, we termed Marginal Zone precursor-like (MZp). We have reported similar observations with HIV-transgenic mice, Simian Immunodeficiency Virus (SIV)-infected macaques, and more recently, with HIV-infected Beninese commercial sex workers, which suggests that excess BAFF and increased frequencies of MZp B-cells are reliable markers of inflammation in the context of HIV. Importantly, we have recently shown that in healthy individuals, MZps present an important regulatory B-cell (Breg) profile and function. Herein, we wish to review our current knowledge on MZ B-cell populations, especially their Breg status, and that of other B-cell populations sharing similar features. BAFF and its analog A Proliferation-Inducing Ligand (APRIL) are important in shaping the MZ B-cell pool; moreover, the impact that excess BAFF—encountered in the context of HIV and several chronic inflammatory conditions—may exert on MZ B-cell populations, Breg and antibody producing capacities is a threat to the self-integrity of their antibody responses and immune surveillance functions. As such, deregulations of MZ B-cell populations contribute to autoimmune manifestations and the development of MZ lymphomas (MZLs) in the context of HIV and other inflammatory diseases. Therefore, further comprehending the mechanisms regulating MZ B-cell populations and their functions could be beneficial to innovative therapeutic avenues that could be deployed to restore MZ B-cell immune competence in the context of chronic inflammation involving excess BAFF.

Multiparametric Tissue Characterization Utilizing the Cellular Metallome and Immuno-Mass Spectrometry Imaging

“…The iron-rich marginal zone also showed higher intensities of CD19 (marker for B-cells) and Arginase-1 (M2 macrophages), while CD86 (M1 macrophages) was expressed to a higher extent in the other regions of the red pulp (Figure S5). These results are in good accordance with the literature, where a high number of B-cells and macrophages was reported in the marginal zone and the red pulps of the spleen, respectively. − However, since the spleen was derived from an immunodeficient mouse model (CB-17/SCID), it has to be mentioned that the B- and T-cell levels were relatively low.…”

Excess BAFF Alters NR4As Expression Levels and Breg Function of Human Precursor-like Marginal Zone B-Cells in the Context of HIV-1 Infection

“…All of which support their influence on several cell types. The capacity of MZ B-cell populations to perform antigen presentation and Breg activity, or to differentiate towards Ig production, may be dictated by the overall situation and environment (reviewed in [ 61 ]).…”

Human B-cell subset identification and changes in inflammatory diseases

“…Also, as MZB depletion in COVID and SLE has been shown to be reversible following resolution of the infection and with treatment respectively, inflammatory factors can result in significant plasticity in this population [ 55 , 135 ]. The functional significance of depletion in MZB is unknown but could underly the increased susceptibility of patients to infection with encapsulated bacteria or defective B regulatory responses [ 140 , 141 ].…”