Germinal Centers Victora, Gabriel D; Nussenzweig, Michel C
Annual review of immunology,
04/2022, Letnik:
40, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Germinal centers (GCs) are microanatomical sites of B cell clonal expansion and antibody affinity maturation. Therein, B cells undergo the Darwinian process of somatic diversification and ...affinity-driven selection of immunoglobulins that produces the high-affinity antibodies essential for effective humoral immunity. Here, we review recent developments in the field of GC biology, primarily as it pertains to GCs induced by infection or immunization. First, we summarize the phenotype and function of the different cell types that compose the GC, focusing on GC B cells. Then, we review the cellular and molecular bases of affinity-dependent selection within the GC and the export of memory and plasma cells. Finally, we present an overview of the emerging field of GC clonal dynamics, focusing on how GC and post-GC selection shapes the diversity of antibodies secreted into serum.
Combination anti-retroviral therapy (ART) has revolutionized the treatment and prevention of HIV-1 infection. Taken daily, ART prevents and suppresses the infection. However, ART interruption almost ...invariably leads to rebound viremia in infected individuals due to a long-lived latent reservoir of integrated proviruses. Therefore, ART must be administered on a life-long basis. Here we review recent preclinical and clinical studies suggesting that immunotherapy may be an alternative or an adjuvant to ART because, in addition to preventing new infections, anti-HIV-1 antibodies clear the virus, directly kill infected cells and produce immune complexes that can enhance host immunity to the virus.
Germinal centers Victora, Gabriel D; Nussenzweig, Michel C
Annual review of immunology,
01/2012, Letnik:
30
Journal Article
Recenzirano
Germinal centers (GCs) were described more than 125 years ago as compartments within secondary lymphoid organs that contained mitotic cells. Since then, it has become clear that this structure is the ...site of B cell clonal expansion, somatic hypermutation, and affinity-based selection, the combination of which results in the production of high-affinity antibodies. Decades of anatomical and functional studies have led to an overall model of how the GC reaction and affinity-based selection operate. More recently, the introduction of intravital imaging into the GC field has opened the door to direct investigation of certain key dynamic features of this microanatomic structure, sparking renewed interest in the relationship between cell movement and affinity maturation. We review these and other recent advances in our understanding of GCs, focusing on cellular dynamics and on the mechanism of selection of high-affinity B cells.
Broadly neutralizing antibodies (bNAbs) against HIV-1 provide both effective pre-exposure prophylaxis and treatment of HIV-1 infection in murine and nonhuman primate models, suggesting their ...potential use in humans. Although much is known about the role of variable domains in the neutralization breadth and potency of these bNAbs, the contribution of Fc domains to their activities is, by contrast, poorly characterized. Assessment of the in vivo activity of several bNAbs revealed that FcγR-mediated effector function contributes substantially to their capacity to block viral entry, suppress viremia, and confer therapeutic activity. Enhanced in vivo potency of anti-HIV-1 bNAbs was associated with preferential engagement of activating, but not inhibitory FcγRs, and Fc domain-engineered bNAb variants with selective binding capacity for activating FcγRs displayed augmented protective activity. These findings reveal key roles for Fc effector function in the in vivo activity of anti-HIV-1 bNAbs and provide strategies for generating bNAbs with improved efficacy.
Dendritic cells (DCs) are specialized antigen-presenting cells and essential mediators of immunity and tolerance. This group of cells is heterogeneous in terms of cell-surface markers, anatomic ...location, and function. Here, we review the development and function of DCs found in lymphoid and non-lymphoid tissues in the steady state. DC and monocyte lineages originate from a common progenitor, the monocyte and dendritic cell progenitor (MDP). The two cell types diverge when MDPs give rise to monocytes and committed DC progenitors (CDPs) in the bone marrow. CDPs give rise to pre-DCs, which migrate from the bone marrow to lymphoid and non-lymphoid tissues to produce the two major subpopulations of lymphoid tissue DCs and non-lymphoid tissue CD103⁺ DCs. Within tissues and during development, DC division and homeostasis are regulated by the hormone Flt3L.
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