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Article ; Online: Oxidized hemoglobin triggers polyreactivity and autoreactivity of human IgG via transfer of heme

Cyril Planchais / Remi Noe / Marie Gilbert / Maxime Lecerf / Srini V. Kaveri / Sébastien Lacroix-Desmazes / Lubka T. Roumenina / Jordan D. Dimitrov

Communications Biology, Vol 6, Iss 1, Pp 1-

2023 Volume 15

Abstract: Oxidized hemoglobin induces polyreactivity and autoreactivity of human IgG through direct transfer and binding of heme to the variable region of IgG, which contributes to a better understanding of the physiopathology of hemolytic diseases. ...

Abstract	Oxidized hemoglobin induces polyreactivity and autoreactivity of human IgG through direct transfer and binding of heme to the variable region of IgG, which contributes to a better understanding of the physiopathology of hemolytic diseases.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Early antiretroviral therapy favors post-treatment SIV control associated with the expansion of enhanced memory CD8+ T-cells

Caroline Passaes / Delphine Desjardins / Anaïs Chapel / Valérie Monceaux / Julien Lemaitre / Adeline Mélard / Federico Perdomo-Celis / Cyril Planchais / Maël Gourvès / Nastasia Dimant / Annie David / Nathalie Dereuddre-Bosquet / Aurélie Barrail-Tran / Hélène Gouget / Céline Guillaume / Francis Relouzat / Olivier Lambotte / Jérémie Guedj / Michaela Müller-Trutwin /

Hugo Mouquet / Christine Rouzioux / Véronique Avettand-Fenoël / Roger Le Grand / Asier Sáez-Cirión

Nature Communications, Vol 15, Iss 1, Pp 1-

2024 Volume 19

Abstract: Abstract HIV remission can be achieved in some people, called post-treatment HIV controllers, after antiretroviral treatment discontinuation. Treatment initiation close to the time of infection was suggested to favor post-treatment control, but the ... ...

Abstract	Abstract HIV remission can be achieved in some people, called post-treatment HIV controllers, after antiretroviral treatment discontinuation. Treatment initiation close to the time of infection was suggested to favor post-treatment control, but the circumstances and mechanisms leading to this outcome remain unclear. Here we evaluate the impact of early (week 4) vs. late (week 24 post-infection) treatment initiation in SIVmac251-infected male cynomolgus macaques receiving 2 years of therapy before analytical treatment interruption. We show that early treatment strongly promotes post-treatment control, which is not related to a lower frequency of infected cells at treatment interruption. Rather, early treatment favors the development of long-term memory CD8+ T cells with enhanced proliferative and SIV suppressive capacity that are able to mediate a robust secondary-like response upon viral rebound. Our model allows us to formally demonstrate a link between treatment initiation during primary infection and the promotion of post-treatment control and provides results that may guide the development of new immunotherapies for HIV remission.
Keywords	Science ; Q
Subject code	616
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Broadly neutralizing anti-HIV-1 antibodies tether viral particles at the surface of infected cells

Jérémy Dufloo / Cyril Planchais / Stéphane Frémont / Valérie Lorin / Florence Guivel-Benhassine / Karl Stefic / Nicoletta Casartelli / Arnaud Echard / Philippe Roingeard / Hugo Mouquet / Olivier Schwartz / Timothée Bruel

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 11

Abstract: Broadly neutralizing antibodies (bNAbs) neutralize HIV-1 and exert Fc-dependent activities against infected cells. Here, Dufloo et al. show that bNAbs also block HIV-1 release by trapping viral particles at the surface of infected cells. ...

Abstract	Broadly neutralizing antibodies (bNAbs) neutralize HIV-1 and exert Fc-dependent activities against infected cells. Here, Dufloo et al. show that bNAbs also block HIV-1 release by trapping viral particles at the surface of infected cells.
Keywords	Science ; Q
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: NK-B cell cross talk induces CXCR5 expression on natural killer cells

Philippe Rascle / Béatrice Jacquelin / Caroline Petitdemange / Vanessa Contreras / Cyril Planchais / Marie Lazzerini / Nathalie Dereuddre-Bosquet / Roger Le Grand / Hugo Mouquet / Nicolas Huot / Michaela Müller-Trutwin

iScience, Vol 24, Iss 10, Pp 103109- (2021)

2021

Abstract: Summary: B cell follicles (BCFs) in lymph nodes (LNs) are generally exempt of CD8+ T and NK cells. African green monkeys (AGMs), a natural host of simian immunodeficiency virus (SIV), display NK cell-mediated viral control in BCF. NK cell migration into ... ...

Abstract	Summary: B cell follicles (BCFs) in lymph nodes (LNs) are generally exempt of CD8+ T and NK cells. African green monkeys (AGMs), a natural host of simian immunodeficiency virus (SIV), display NK cell-mediated viral control in BCF. NK cell migration into BCF in chronically SIVagm-infected AGM is associated with CXCR5+ NK cells. We aimed to identify the mechanism leading to CXCR5 expression on NK cells. We show that CXCR5+ NK cells in LN were induced following SIVagm infection. CXCR5+ NK cells accumulated preferentially in BCF with proliferating B cells. Autologous NK-B cell co-cultures in transwell chambers induced CXCR5+ NK cells. Transcriptome analysis of CXCR5+ NK cells revealed expression of bcl6 and IL6R. IL-6 induced CXCR5 on AGM and human NK cells. IL6 mRNA was detected in LN at higher levels during SIVagm than SIVmac infection and often produced by plasma cells. Our study reveals a mechanism of B cell-dependent NK cell regulation.
Keywords	immunology ; virology ; Science ; Q
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies

Cell Reports Medicine, Vol 2, Iss 5, Pp 100275- (2021)

2021

Abstract: Summary: Many SARS-CoV-2-infected individuals remain asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyze antibody functions in 52 asymptomatic infected individuals, 119 mildly symptomatic, and ... ...

Abstract	Summary: Many SARS-CoV-2-infected individuals remain asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyze antibody functions in 52 asymptomatic infected individuals, 119 mildly symptomatic, and 21 hospitalized patients with COVID-19. We measure anti-spike immunoglobulin G (IgG), IgA, and IgM levels with the S-Flow assay and map IgG-targeted epitopes with a Luminex assay. We also evaluate neutralization, complement deposition, and antibody-dependent cellular cytotoxicity (ADCC) using replication-competent SARS-CoV-2 or reporter cell systems. We show that COVID-19 sera mediate complement deposition and kill infected cells by ADCC. Sera from asymptomatic individuals neutralize the virus, activate ADCC, and trigger complement deposition. Antibody levels and functions are lower in asymptomatic individuals than they are in symptomatic cases. Antibody functions are correlated, regardless of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction. Overall, asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells.
Keywords	SARS-CoV-2 ; ADCC ; complement ; asymptomatic ; antibody ; Medicine (General) ; R5-920
Subject code	570
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fusogenicity and neutralization sensitivity of the SARS-CoV-2 Delta sublineage AY.4.2

Nell Saunders / Delphine Planas / William H. Bolland / Christophe Rodriguez / Slim Fourati / Julian Buchrieser / Cyril Planchais / Matthieu Prot / Isabelle Staropoli / Florence Guivel-Benhassine / Françoise Porrot / David Veyer / Hélène Péré / Nicolas Robillard / Madelina Saliba / Artem Baidaliuk / Aymeric Seve / Laurent Hocqueloux / Thierry Prazuck /

Felix A. Rey / Hugo Mouquet / Etienne Simon-Lorière / Timothée Bruel / Jean-Michel Pawlotsky / Olivier Schwartz

EBioMedicine, Vol 77, Iss , Pp 103934- (2022)

2022

Abstract: Summary: Background: SARS-CoV-2 lineages are continuously evolving. As of December 2021, the AY.4.2 Delta sub-lineage represented 20 % of sequenced strains in the UK and had been detected in dozens of countries. It has since then been supplanted by ... ...

Abstract	Summary: Background: SARS-CoV-2 lineages are continuously evolving. As of December 2021, the AY.4.2 Delta sub-lineage represented 20 % of sequenced strains in the UK and had been detected in dozens of countries. It has since then been supplanted by Omicron. The AY.4.2 spike displays three additional mutations (T95I, Y145H and A222V) in the N-terminal domain when compared to the original Delta variant (B.1.617.2) and remains poorly characterized. Methods: We compared the Delta and the AY.4.2 spikes, by assessing their binding to antibodies and ACE2 and their fusogenicity. We studied the sensitivity of an authentic AY.4.2 viral isolate to neutralizing antibodies. Findings: The AY.4.2 spike exhibited similar binding to all the antibodies and sera tested, and similar fusogenicity and binding to ACE2 than the ancestral Delta spike. The AY.4.2 virus was slightly less sensitive than Delta to neutralization by a panel of monoclonal antibodies; noticeably, the anti-RBD Imdevimab showed incomplete neutralization. Sensitivity of AY.4.2 to sera from vaccinated individuals was reduced by 1.3 to 3-fold, when compared to Delta. Interpretation: Our results suggest that mutations in the NTD remotely impair the efficacy of anti-RBD antibodies. The spread of AY.4.2 was not due to major changes in spike fusogenicity or ACE2 binding, but more likely to a partially reduced neutralization sensitivity. Funding: The work was funded by Institut Pasteur, Fondation pour la Recherche Médicale, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, ANRS, the Vaccine Research Institute, Labex IBEID, ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR.
Keywords	SARS-CoV-2 ; Delta ; AY.4.2 ; Vaccines ; Fusogenicity ; Neutralization ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	570
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Tocilizumab-treated convalescent COVID-19 patients retain the cross-neutralization potential against SARS-CoV-2 variants

Camille Chauvin / Laurine Levillayer / Mathilde Roumier / Hubert Nielly / Claude Roth / Anupama Karnam / Srinivasa Reddy Bonam / Anne Bourgarit / Clément Dubost / Aurore Bousquet / Sébastien Le Burel / Raphaële Mestiri / Damien Sene / Joris Galland / Marc Vasse / Matthieu Groh / Mathilde Le Marchand / Camille Vassord-Dang / Jean-François Gautier /

Nhan Pham-Thi / Christiane Verny / Bruno Pitard / Cyril Planchais / Hugo Mouquet / Richard Paul / Etienne Simon-Loriere / Jagadeesh Bayry / Laurent Gilardin / Anavaj Sakuntabhai

iScience, Vol 26, Iss 3, Pp 106124- (2023)

2023

Abstract: Summary: Although tocilizumab treatment in severe and critical coronavirus disease 2019 (COVID-19) patients has proven its efficacy at the clinical level, there is little evidence supporting the effect of short-term use of interleukin-6 receptor blocking ...

Abstract	Summary: Although tocilizumab treatment in severe and critical coronavirus disease 2019 (COVID-19) patients has proven its efficacy at the clinical level, there is little evidence supporting the effect of short-term use of interleukin-6 receptor blocking therapy on the B cell sub-populations and the cross-neutralization of SARS-CoV-2 variants in convalescent COVID-19 patients. We performed immunological profiling of 69 tocilizumab-treated and non-treated convalescent COVID-19 patients in total. We observed that SARS-CoV-2-specific IgG1 titers depended on disease severity but not on tocilizumab treatment. The plasma of both treated and non-treated patients infected with the ancestral variant exhibit strong neutralizing activity against the ancestral virus and the Alpha, Beta, and Delta variants of SARS-CoV-2, whereas the Gamma and Omicron viruses were less sensitive to seroneutralization. Overall, we observed that, despite the clinical benefits of short-term tocilizumab therapy in modifying the cytokine storm associated with COVID-19 infections, there were no modifications in the robustness of B cell and IgG responses to Spike antigens.
Keywords	Health sciences ; Virology ; treatment ; Immunology ; Science ; Q
Subject code	616
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity

Julie Prigent / Annaëlle Jarossay / Cyril Planchais / Caroline Eden / Jérémy Dufloo / Ayrin Kök / Valérie Lorin / Oxana Vratskikh / Thérèse Couderc / Timothée Bruel / Olivier Schwartz / Michael S. Seaman / Oliver Ohlenschläger / Jordan D. Dimitrov / Hugo Mouquet

Cell Reports, Vol 23, Iss 9, Pp 2568-

2018 Volume 2581

Abstract: Human high-affinity antibodies to pathogens often recognize unrelated ligands. The molecular origin and the role of this polyreactivity are largely unknown. Here, we report that HIV-1 broadly neutralizing antibodies (bNAbs) are frequently polyreactive, ... ...

Abstract	Human high-affinity antibodies to pathogens often recognize unrelated ligands. The molecular origin and the role of this polyreactivity are largely unknown. Here, we report that HIV-1 broadly neutralizing antibodies (bNAbs) are frequently polyreactive, cross-reacting with non-HIV-1 molecules, including self-antigens. Mutating bNAb genes to increase HIV-1 binding and neutralization also results in de novo polyreactivity. Unliganded paratopes of polyreactive bNAbs with improved HIV-1 neutralization exhibit a conformational flexibility, which contributes to enhanced affinity of bNAbs to various HIV-1 envelope glycoproteins and non-HIV antigens. Binding adaptation of polyreactive bNAbs to the divergent ligands mainly involves hydrophophic interactions. Plasticity of bNAbs’ paratopes may, therefore, facilitate accommodating divergent viral variants, but it simultaneously triggers promiscuous binding to non-HIV-1 antigens. Thus, a certain level of polyreactivity can be a mark of adaptable antibodies displaying optimal pathogens’ recognition.
Keywords	antibody ; B cells ; HIV-1 ; polyreactivity ; autoreactivity ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2018-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: HIV-1 Envelope Recognition by Polyreactive and Cross-Reactive Intestinal B Cells

Cyril Planchais / Ayrin Kök / Alexia Kanyavuz / Valérie Lorin / Timothée Bruel / Florence Guivel-Benhassine / Tim Rollenske / Julie Prigent / Thierry Hieu / Thierry Prazuck / Laurent Lefrou / Hedda Wardemann / Olivier Schwartz / Jordan D. Dimitrov / Laurent Hocqueloux / Hugo Mouquet

Cell Reports, Vol 27, Iss 2, Pp 572-585.e

2019 Volume 7

Abstract: Summary: Mucosal immune responses to HIV-1 involve the recognition of the viral envelope glycoprotein (gp)160 by tissue-resident B cells and subsequent secretion of antibodies. To characterize the B cells “sensing” HIV-1 in the gut of infected ... ...

Abstract	Summary: Mucosal immune responses to HIV-1 involve the recognition of the viral envelope glycoprotein (gp)160 by tissue-resident B cells and subsequent secretion of antibodies. To characterize the B cells “sensing” HIV-1 in the gut of infected individuals, we probed monoclonal antibodies produced from single intestinal B cells binding to recombinant gp140 trimers. A large fraction of mucosal B cell antibodies were polyreactive and showed only low affinity to HIV-1 envelope glycoproteins, particularly the gp41 moiety. A few high-affinity gp140 antibodies were isolated but lacked neutralizing, potent ADCC, and transcytosis-blocking capacities. Instead, they displayed cross-reactivity with defined self-antigens. Specifically, intestinal HIV-1 gp41 antibodies targeting the heptad repeat 2 region (HR2) cluster II cross-reacted with the p38α mitogen-activated protein kinase 14 (MAPK14). Hence, physiologic polyreactivity of intestinal B cells and molecular mimicry-based self-reactivity of HIV-1 antibodies are two independent phenomena, possibly diverting and/or impairing mucosal humoral immunity to HIV-1. : Antibodies produced in mucosa after sexual transmission of HIV-1 could affect viral propagation. Planchais et al. show that intestinal B cells from HIV-1-infected individuals that recognize the HIV-1 envelope (Env) proteins are mainly low affinity and polyreactive and that rare, high-affinity antibodies to HIV-1 Env lack potent antiviral capacities and cross-react with self-antigens. Keywords: HIV-1, antibodies, B cells, mucosa, polyreactivity, cross-reactivity, MAPK14, intestine
Keywords	Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Cryptic polyreactivity of IgG expressed by splenic marginal zone B-cell lymphoma

Mahendra, Ankit / Bagirath Gangadharan / Cyril Planchais / FrÃ©dÃ©ric Davi / Jordan D. Dimitrov / Maxime Lecerf / Myriam Boudjoghra / SÃ©bastien AndrÃ© / SÃ©bastien Lacroix-Desmazes / Srinivas V. Kaveri

Molecular Immunology. 2014 July, v. 60

2014

Abstract: Polyreactive antibodies represent a significant fraction of immune repertoires and play an important role in the immune defense and immune homeostasis. Polyreactive B-cell receptors (BCR), however, are frequently expressed by B-cell lymphomas. It was ... ...

Abstract	Polyreactive antibodies represent a significant fraction of immune repertoires and play an important role in the immune defense and immune homeostasis. Polyreactive B-cell receptors (BCR), however, are frequently expressed by B-cell lymphomas. It was suggested that polyreactive BCR on lymphoma cells might deliver stimulation signals by binding to various endogenous or exogenous antigens, thus promoting the survival of the malignant cells. In addition to natural polyreactive antibodies, immune repertoires contain antibodies that acquire polyreactivity after exposure to different redox-active substances such as reactive oxygen species, iron ions and heme. Here, we demonstrate that an antibody cloned from a patient's splenic marginal zone B-cell lymphoma acquires physiologically relevant binding affinity to various autoantigens following exposure to heme. We elucidated the mechanisms underlying polyreactive antigen binding. The results obtained in this study imply that antigen-binding receptors expressed on some malignant cells acquire polyreactivity after exposure to redox substances that are released at sites of inflammation or as a result of cellular damage. The acquisition of novel BCR specificities under hemolytic or inflammatory conditions may play an important role in the physiopathology of certain B-cell malignancies.
Keywords	antibodies ; autoantigens ; binding capacity ; B-lymphocytes ; heme ; homeostasis ; immune response ; immunoglobulin G ; inflammation ; ions ; lymphoma ; neoplasm cells ; pathophysiology ; patients ; reactive oxygen species ; receptors
Language	English
Dates of publication	2014-07
Size	p. 54-61.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2014.03.009
Database	NAL-Catalogue (AGRICOLA)

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