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Related Concept Videos

Cells of the Adaptive Immune Response01:23

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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
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Primary lymphoid organs are pivotal in the formation, development, and maturation of lymphocytes, the white blood cells that serve as the backbone of our immune system. This crucial function underscores their fundamental role in maintaining our overall health and immunity. The two primary lymphoid organs of prime importance are the red bone marrow and the thymus.
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The initiation of cell-mediated immunity can be observed as early as the third month of fetal growth, with active antibody-mediated immunity following approximately one month later.
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Long-primed germinal centres with enduring affinity maturation and clonal migration.

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Long-term germinal center B cells (BGC) sustained for over six months after initial immunization, showing continuous antibody evolution and leading to high-titer neutralizing antibodies after boosting. This long-prime immunization strategy benefits challenging vaccine targets.

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Area of Science:

  • Immunology
  • Vaccinology

Background:

  • Germinal centers (GCs) are crucial for adaptive immune responses and antibody maturation.
  • The duration and activity of GC B cells (BGC) are critical for generating high-affinity antibodies, especially against complex antigens like HIV Env.
  • Understanding long-term GC dynamics is essential for designing effective vaccines against challenging pathogens.

Purpose of the Study:

  • To investigate the longevity and functional characteristics of germinal center B cells (BGC) following a prolonged primary immunization with HIV Env protein in rhesus monkeys.
  • To assess the impact of extended GC activity on antibody somatic hypermutation, epitope recognition, and neutralizing antibody responses.
  • To evaluate the potential of a long-prime, slow-delivery immunization strategy for overcoming immunodominance challenges in vaccine development.

Main Methods:

  • Rhesus monkeys were primed with HIV Env protein and monitored for up to 29 weeks without further antigen exposure.
  • Single-cell transcriptional profiling was employed to analyze the states of GC B cells (BGC).
  • Antibody somatic hypermutation and BGC cell lineage phylogenies were analyzed to track B cell evolution and selection.

Main Results:

  • Sustained populations of germinal center B cells (BGC) were observed for at least 6 months, with a significant increase in BGC cells by week 10.
  • Single-cell profiling confirmed the maintenance of both light- and dark-zone GC states, with ongoing antibody somatic hypermutation and selection.
  • Env-binding BGC cells remained elevated at 29 weeks, and a single booster immunization elicited high titers of HIV-neutralizing antibodies.
  • Memory B cells generated under long-prime conditions exhibited higher somatic hypermutation and recognized non-immunodominant epitopes.

Conclusions:

  • Prolonged GC activity, sustained for over 6 months without re-immunization, can be achieved through a long-prime immunization approach.
  • This extended GC phase promotes significant antibody evolution, leading to potent neutralizing antibody responses against complex antigens.
  • The long-prime, slow-delivery immunization strategy shows promise for developing vaccines against difficult targets by optimizing GC tuning for maximal antibody responses.