ArticlePloS one2009
Functional, non-clonal IgMa-restricted B cell receptor interactions with the HIV-1 envelope gp41 membrane proximal external region.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- 9G4+ antibodies isolated from HIV-infected patients neutralize HIV-1 and have distinct autoreactivity profiles.PloS one · 2013Trial
- Bacterial lectin BambL acts as a B cell superantigen.Cellular and molecular life sciences : CMLS · 2021Article
- Continuous Culture of Mouse Primary B Lymphocytes by Forced Expression ofJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- Immunologic characteristics of HIV-infected individuals who make broadly neutralizing antibodies.Immunological reviews · 2017Review
- Immune perturbations in HIV-1-infected individuals who make broadly neutralizing antibodies.Science immunology · 2016Article
- Efficient role of IgH 3' regulatory region deficient B-cells in the development of oil granulomas.Oncotarget · 2016Article
- Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages.Science translational medicine · 2016Article
- Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques.PLoS pathogens · 2015Article
- Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Modulation of nonneutralizing HIV-1 gp41 responses by an MHC-restricted TH epitope overlapping those of membrane proximal external region broadly neutralizing antibodies.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Induction of HIV-1 broad neutralizing antibodies in 2F5 knock-in mice: selection against membrane proximal external region-associated autoreactivity limits T-dependent responses.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Common tolerance mechanisms, but distinct cross-reactivities associated with gp41 and lipids, limit production of HIV-1 broad neutralizing antibodies 2F5 and 4E10.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Clonal analysis of human anti-V3 monoclonal antibodies selected by a V3 tetramer.Human antibodies · 2012Article
- Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.The Journal of experimental medicine · 2011Article
- Rescue of HIV-1 broad neutralizing antibody-expressing B cells in 2F5 VH x VL knockin mice reveals multiple tolerance controls.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Role of immune mechanisms in induction of HIV-1 broadly neutralizing antibodies.Current opinion in immunology · 2011Review
- Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting.PloS one · 2011Article
- A versatile vector for the production of pseudotyped viruses expressing gp120 antigens from different clades of primary HIV-1 isolates.Journal of virological methods · 2011Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The membrane proximal external region (MPER) of HIV-1 gp41 has several features that make it an attractive antibody-based vaccine target, but eliciting an effective gp41 MPER-specific protective antibody response remains elusive. One fundamental issue is whether the failure to make gp41 MPER-specific broadly neutralizing antibodies like 2F5 and 4E10 is due to structural constraints with the gp41 MPER, or alternatively, if gp41 MPER epitope-specific B cells are lost to immunological tolerance. An equally important question is how B cells interact with, and respond to, the gp41 MPER epitope, including whether they engage this epitope in a non-canonical manner i.e., by non-paratopic recognition via B cell receptors (BCR). To begin understanding how B cells engage the gp41 MPER, we characterized B cell-gp41 MPER interactions in BALB/c and C57BL/6 mice. Surprisingly, we found that a significant (approximately 7%) fraction of splenic B cells from BALB/c, but not C57BL/6 mice, bound the gp41 MPER via their BCRs. This strain-specific binding was concentrated in IgM(hi) subsets, including marginal zone and peritoneal B1 B cells, and correlated with enriched fractions (approximately 15%) of gp41 MPER-specific IgM secreted by in vitro-activated splenic B cells. Analysis of Igh(a) (BALB/c) and Igh(b) (C57BL/6) congenic mice demonstrated that gp41 MPER binding was controlled by determinants of the Igh(a) locus. Mapping of MPER gp41 interactions with IgM(a) identified MPER residues distinct from those to which mAb 2F5 binds and demonstrated the requirement of Fc C(H) regions. Importantly, gp41 MPER ligation produced detectable BCR-proximal signaling events, suggesting that interactions between gp41 MPER and IgM(a) determinants may elicit partial B cell activation. These data suggest that low avidity, non-paratopic interactions between the gp41 MPER and membrane Ig on naïve B cells may interfere with or divert bnAb responses.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.