Related Experiment Video
Updated: Nov 9, 2025
14:23
A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
15.9K
Distinct clonal evolution of B-cells in HIV controllers with neutralizing antibody breadth.
Deniz Cizmeci1, Giuseppe Lofano1, Evan Rossignol1
1Ragon Institute of MGH, MIT and Harvard, Cambridge, United States.
Elife
|April 12, 2021
Summary
Investigating HIV controllers revealed that B-cell receptor (BCR) mutations correlate with antibody neutralization breadth. This suggests host factors, not just high viral load, may drive potent HIV antibody responses, informing future vaccine development.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Antibody neutralization breadth against HIV-1 is rare during natural infection, often linked to high viral loads.
- Vaccine strategies have struggled to elicit similar breadth, with mechanisms of neutralizing antibody induction remaining unclear.
- Broadly neutralizing antibodies are also found in HIV controllers with low viral loads, challenging the necessity of high antigen exposure.
Purpose of the Study:
- To analyze B-cell receptor (BCR) repertoires in HIV controllers to identify factors associated with neutralizing antibody breadth.
- To investigate the relationship between BCR immunoglobulin gene repertoire alterations, clonal expansions, and neutralization breadth in individuals controlling HIV-1.
Main Methods:
- Analysis of paired heavy and light chain BCR repertoires from 12,591 HIV-1 envelope-specific single memory B-cells.
- Studied 22 individuals with HIV who naturally control the virus to low or undetectable plasma levels without antiretroviral therapy.
- Correlated genomic mutation frequencies in IGHV and IGLV genes with serum neutralization breadth.
Main Results:
- A direct correlation was observed between the frequency of genomic mutations in IGHV and IGLV genes and serum neutralization breadth.
- The most mutated antibody repertoires were characterized by a few large clones exhibiting evolutionary signatures of peak affinity maturation.
- These findings indicate that extensive somatic hypermutation and clonal evolution can occur even with low HIV antigen levels.
Conclusions:
- BCR selection for extended somatic hypermutation and clonal evolution can occur in HIV controllers with low antigen exposure.
- Host-specific factors, rather than solely high antigen load, may play a crucial role in developing neutralizing antibody breadth.
- These insights could guide the development of future HIV vaccine strategies targeting host-specific mechanisms.
Related Concept Videos
01:22T Cell Activation and Clonal Selection
13.8K
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
13.8K
01:24B Cell Activation and Differentiation
14.9K
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.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
14.9K
01:23Cells of the Adaptive Immune Response
7.3K
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...
7.3K
01:29Immune Response Against Viral Pathogens
1.2K
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
1.2K
01:20Special Features of Adaptive Immunity
1.6K
The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
1.6K