Recall Germinal Center and Antibody Responses
type: CreativeWork
description: Repeated exposure to viruses or their antigens elicits anamnestic antibody responses that produce antibodies that are of greater magnitude and affinity compared to those induced after primary exposure to antigen.The anamnestic nature of the response is a result of the recall of memory B cells (MBCs) that have undergone clonal expansion and affinity maturation in germinal centers(GCs) during the primary response. Upon antigen re-encounter ("boosting"), MBCs, aided by enhanced help from memory T cells, efficiently differentiate into antibody-secreting plasma cells. At the same time, boosting induces recall GCs that could in principle either further affinity mature primary-derived MBCs or engage naïve B cells with potentially new epitope-specificities. The balance between these two possibilities is important for the rational design of vaccine strategies that can induce broadly neutralizing antibodies against mutating viruses like HIV-1, influenza A virus and SARS-CoV-2. Moreover, it is important in the context of a serum phenomenon termed antigenic imprinting or "original antigenic sin" (OAS), in which the antibody response is thought to repeatedly derive from the first cohort of B cells engaged by primary antigenic exposure, at the expense of inducing de novo antibodies against related antigens. Recall antibody responses therefore emerge from a complex interplay of B cell clones with varying degrees of specificity, affinity maturation and via intercalating MBC stages. The response is further affected by T cell help and potentially shaped by the competition of B cells with pre-existing antibodies for access to antigen (antibody-mediated feedback). Our studies, employing various prime-boost models in genetic fate-mapping mice, address multiple aspects of the recall B cell and antibody response. First, using cellular fate-mapping in which we mark the primary-cohort B cells and their MBC progeny with fluorescent proteins, we addressed the contribution of MBC clones to the…
abstract: Repeated exposure to viruses or their antigens elicits anamnestic antibody responses that produce antibodies that are of greater magnitude and affinity compared to those induced after primary exposure to antigen.The anamnestic nature of the response is a result of the recall of memory B cells (MBCs) that have undergone clonal expansion and affinity maturation in germinal centers(GCs) during the primary response. Upon antigen re-encounter ("boosting"), MBCs, aided by enhanced help from memory T cells, efficiently differentiate into antibody-secreting plasma cells. At the same time, boosting induces recall GCs that could in principle either further affinity mature primary-derived MBCs or engage naïve B cells with potentially new epitope-specificities. The balance between these two possibilities is important for the rational design of vaccine strategies that can induce broadly neutralizing antibodies against mutating viruses like HIV-1, influenza A virus and SARS-CoV-2. Moreover, it is important in the context of a serum phenomenon termed antigenic imprinting or "original antigenic sin" (OAS), in which the antibody response is thought to repeatedly derive from the first cohort of B cells engaged by primary antigenic exposure, at the expense of inducing de novo antibodies against related antigens. Recall antibody responses therefore emerge from a complex interplay of B cell clones with varying degrees of specificity, affinity maturation and via intercalating MBC stages. The response is further affected by T cell help and potentially shaped by the competition of B cells with pre-existing antibodies for access to antigen (antibody-mediated feedback). Our studies, employing various prime-boost models in genetic fate-mapping mice, address multiple aspects of the recall B cell and antibody response. First, using cellular fate-mapping in which we mark the primary-cohort B cells and their MBC progeny with fluorescent proteins, we addressed the contribution of MBC clones to the…
author: Schiepers, Ariën
keywords: antibody recall, memory B cells, antigenic imprinting, germinal centers, affinity maturation, vaccine design, Life Sciences
date published: 2024-01-01T08:00:00Z
date modified: 2026-07-24T04:11:21Z
provider: Rockefeller
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Rockefeller