Featured
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Article |
Bone marrow plasma cells require P2RX4 to sense extracellular ATP
We demonstrate the role of the ligand-gated purinergic ion channel P2RX4 in maintaining mouse plasma cells in their bone marrow niche.
- Masaki Ishikawa
- , Zainul S. Hasanali
- & Avinash Bhandoola
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Article
| Open Access
Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting
Exposure to early variants of SARS-CoV-2 results in immune imprinting in mouse models and in humans, reducing neutralizing antibody titres against Omicron variants, which could be mitigated with multiple updated boosters.
- Ayijiang Yisimayi
- , Weiliang Song
- & Yunlong Cao
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Article
| Open Access
Distinguishing features of long COVID identified through immune profiling
Individuals with long COVID show marked biological changes in cortisol and immune factors relative to convalescent populations.
- Jon Klein
- , Jamie Wood
- & Akiko Iwasaki
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Article
| Open Access
Neutralization, effector function and immune imprinting of Omicron variants
Convergent mutations in hot spots of the spike proteins of currently circulating SARS-CoV-2 Omicron variants increase the binding affinity for the host receptor and promote more efficient fusion with host cell membranes.
- Amin Addetia
- , Luca Piccoli
- & David Veesler
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Article |
SARS-CoV-2 Omicron boosting induces de novo B cell response in humans
COVID-19 booster immunizations aimed at spike protein from new SARS-CoV-2 variants induce robust germinal centre B cell responses against the original spike protein, as well as de novo B cell responses against the variant spike protein.
- Wafaa B. Alsoussi
- , Sameer Kumar Malladi
- & Ali H. Ellebedy
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Article |
Immunoglobulin M perception by FcμR
The structural basis for the molecular mechanism of recognition of different IgM forms by the IgM receptor FcμR is determined using crystallography and cryo-electron microscopy.
- Yaxin Li
- , Hao Shen
- & Junyu Xiao
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Article |
Molecular fate-mapping of serum antibody responses to repeat immunization
Serum antibody responses to sequential homologous booster vaccines derive overwhelmingly from primary cohort B cells at the expense of de novo responses; this ‘primary addiction’ can be overcome by boosting with variant antigens.
- Ariën Schiepers
- , Marije F. L. van ’t Wout
- & Gabriel D. Victora
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Article
| Open Access
Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution
Convergent mutations in hotspots of the SARS-CoV-2 Omicron receptor-binding domain can cause immune evasion and maintain sufficient ACE2-binding capability.
- Yunlong Cao
- , Fanchong Jian
- & Xiaoliang Sunney Xie
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Article
| Open Access
Antibody feedback regulates immune memory after SARS-CoV-2 mRNA vaccination
Pre-existing high-affinity antibodies alter germinal centre and memory B cell selection by lowering the activation threshold for B cells and through direct masking of their cognate epitopes, thereby permitting a diverse set of abundant lower-affinity clones targeting alternate epitopes to participate in the immune response.
- Dennis Schaefer-Babajew
- , Zijun Wang
- & Michel C. Nussenzweig
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Article |
Long-primed germinal centres with enduring affinity maturation and clonal migration
Using HIV Env protein immunogen priming in rhesus monkeys followed by a long period without further immunization, we demonstrate germinal centre B cells lasting at least 6 months, showing promise in regard to difficult vaccine targets.
- Jeong Hyun Lee
- , Henry J. Sutton
- & Shane Crotty
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Article
| Open Access
Dysregulated naive B cells and de novo autoreactivity in severe COVID-19
Single-cell B cell repertoire analysis identifies the expansion of a naive-derived population of antibody-secreting cells contributing to de novo autoreactivity in patients with severe COVID-19 and those with post-COVID symptoms.
- Matthew C. Woodruff
- , Richard P. Ramonell
- & Ignacio Sanz
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Article
| Open Access
BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection
Biochemical and structural studies of the interactions between antibodies and spike proteins from SARS-CoV-2 Omicron subvariants indicate how these variants have evolved to escape antibody-mediated neutralization.
- Yunlong Cao
- , Ayijiang Yisimayi
- & Xiaoliang Sunney Xie
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Article
| Open Access
Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost
A third dose of an mRNA vaccine against SARS-CoV-2 results in an expanded B cell repertoire that produces antibodies with increased potency and breadth.
- Frauke Muecksch
- , Zijun Wang
- & Michel C. Nussenzweig
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Article |
Germinal centre-driven maturation of B cell response to mRNA vaccination
Sequencing of B cell receptors and expression of the corresponding monoclonal antibodies is used to characterize the evolution of the long-term B cell response to SARS-CoV-2 mRNA vaccination.
- Wooseob Kim
- , Julian Q. Zhou
- & Ali H. Ellebedy
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Article
| Open Access
Broadly neutralizing antibodies target a haemagglutinin anchor epitope
A distinct class of broadly neutralizing antibodies to the influenza virus target a membrane-proximal anchor epitope of the haemagglutinin stalk domain.
- Jenna J. Guthmiller
- , Julianna Han
- & Patrick C. Wilson
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Article |
Considerable escape of SARS-CoV-2 Omicron to antibody neutralization
An isolate of the Omicron variant of SARS-COV-2 was completely or partially resistant to neutralization by all nine clinically approved monoclonal antibodies tested.
- Delphine Planas
- , Nell Saunders
- & Olivier Schwartz
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Article |
Parallelism of intestinal secretory IgA shapes functional microbial fitness
The functional role of intestinal secretory IgA for host–microbiota interactions is investigated, showing that intestinal bacterial exposure leads to selection of diverse plasma cells that secrete antigen-specific IgA, which predominantly targets bacterial membranes.
- Tim Rollenske
- , Sophie Burkhalter
- & Andrew J. Macpherson
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Article |
Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity
Immune analyses against circulating SARS-CoV-2 variants show that mRNA vaccination induces robust neutralizing antibodies and boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection.
- Carolina Lucas
- , Chantal B. F. Vogels
- & Akiko Iwasaki
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Article
| Open Access
Anti-SARS-CoV-2 receptor-binding domain antibody evolution after mRNA vaccination
Individual memory antibodies selected over time by natural infection with SARS-CoV-2 have greater potency and breadth than antibodies elicited by vaccination, whereas the overall neutralizing potency of plasma is greater following vaccination.
- Alice Cho
- , Frauke Muecksch
- & Michel C. Nussenzweig
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Article |
Lectins enhance SARS-CoV-2 infection and influence neutralizing antibodies
C-type lectins and SIGLEC1 function as attachment receptors for SARS-CoV-2 and enhance ACE2-mediated infection.
- Florian A. Lempp
- , Leah B. Soriaga
- & Davide Corti
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Article |
SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape
A survey of SARS-CoV-2 RBD antibodies identifies those with activity against diverse SARS-CoV-2 variants and SARS-related coronaviruses, highlighting epitopes and features to prioritize in antibody and vaccine development.
- Tyler N. Starr
- , Nadine Czudnochowski
- & Gyorgy Snell
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Article |
Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization
The SARS-CoV-2 Delta variant partially evades neutralization by several monoclonal antibodies and by sera from individuals who have had COVID-19, but two doses of anti-COVID-19 vaccines still generate a strong neutralizing response.
- Delphine Planas
- , David Veyer
- & Olivier Schwartz
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Article
| Open Access
Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2
Individuals over eighty years of age are less likely to mount a good immune response against SARS-CoV-2 (measured by neutralization titres) after the first dose of the BNT162b2 mRNA vaccine, but achieve good neutralization after the second dose.
- Dami A. Collier
- , Isabella A. T. M. Ferreira
- & Ravindra K. Gupta
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Article |
SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses
Analysis of antigen-specific B cells in lymph nodes of individuals vaccinated with BNT162b2 reveals lasting germinal centre responses, explaining the robust humoral immunity induced by SARS-CoV-2 mRNA-based vaccines.
- Jackson S. Turner
- , Jane A. O’Halloran
- & Ali H. Ellebedy
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Article |
In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains
Experiments in mouse and hamster models show that monoclonal antibody combinations, using antibodies that correspond to products in clinical development, largely retain their efficacy in protecting against currently prevailing variant strains of SARS-CoV-2.
- Rita E. Chen
- , Emma S. Winkler
- & Michael S. Diamond
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Article
| Open Access
Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection
Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.
- Zijun Wang
- , Frauke Muecksch
- & Michel C. Nussenzweig
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Article |
Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants
An engineered IgM antibody administered intranasally in mice shows high prophylactic efficacy and therapeutic efficacy against SARS-CoV-2, and is also effective against multiple variants of concern that are resistant to IgG-based therapeutics.
- Zhiqiang Ku
- , Xuping Xie
- & Zhiqiang An
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Article |
SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans
SARS-CoV-2 infection induces long-lived bone marrow plasma cells that correlate with anti-SARS-CoV-2 spike protein antibody titres in individuals who have recovered from COVID-19.
- Jackson S. Turner
- , Wooseob Kim
- & Ali H. Ellebedy
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Article |
Structural basis of malaria RIFIN binding by LILRB1-containing antibodies
Plasmodium antigens called RIFINs bind to specific antibodies that incorporate the inhibitory receptor LILRB1 through its D3 domain, illustrating the principle of receptor-containing antibodies.
- Yiwei Chen
- , Kai Xu
- & Antonio Lanzavecchia
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Article |
Affinity-coupled CCL22 promotes positive selection in germinal centres
CCL22 promotes positive selection in germinal centres by highlighting affinity-enhanced B cells for helper T cells to sense and seek remotely.
- Bo Liu
- , Yihan Lin
- & Hai Qi
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Article |
mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
The Moderna (mRNA-1273) and Pfizer–BioNTech (BNT162b2) vaccines elicit anti-RBD antibodies similar to those elicited through natural infection with SARS-CoV-2, but their potent neutralizing activity was reduced or abolished by new viral variants of concern.
- Zijun Wang
- , Fabian Schmidt
- & Michel C. Nussenzweig
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Article |
Evolution of antibody immunity to SARS-CoV-2
In a cohort of 87 individuals with COVID-19, the memory B cell response at 6.2 months after the onset of disease evolves in a manner that is consistent with the persistence of SARS-CoV-2 antigen.
- Christian Gaebler
- , Zijun Wang
- & Michel C. Nussenzweig
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Article |
Correlates of protection against SARS-CoV-2 in rhesus macaques
Adoptive transfer of purified IgG from convalescent macaques protects naive macaques against SARS-CoV-2 infection, and cellular immune responses contribute to protection against rechallenge with SARS-CoV-2.
- Katherine McMahan
- , Jingyou Yu
- & Dan H. Barouch
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Article |
ALDH4A1 is an atherosclerosis auto-antigen targeted by protective antibodies
An autoantibody found in a mouse model of atherosclerosis recognizses ALDH4A1, and infusion of the antibody delays plaque formation in mice.
- Cristina Lorenzo
- , Pilar Delgado
- & Almudena R. Ramiro
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Article |
Defining HPV-specific B cell responses in patients with head and neck cancer
Detailed analyses of B cells in the tumour microenvironment of human papilloma virus (HPV)-linked head and neck cancers reveal strong humoral immune responses to HPV antigens and the secretion of HPV-specific antibodies in situ.
- Andreas Wieland
- , Mihir R. Patel
- & Rafi Ahmed
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Article |
Repeated cross-sectional sero-monitoring of SARS-CoV-2 in New York City
Seropositive samples of SARS-CoV-2 were detected as early as mid-February in patients at Mount Sinai Hospital in New York City, and antibody positivity increased during the first wave of the pandemic and remained stable afterwards.
- Daniel Stadlbauer
- , Jessica Tan
- & Florian Krammer
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Article |
Tunable dynamics of B cell selection in gut germinal centres
Antibody selection and maturation within B cells found in gut-associated germinal centres is stimulated by the gut microbiota, to a degree that depends on the presence and composition of the microbes.
- Carla R. Nowosad
- , Luka Mesin
- & Gabriel D. Victora
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Article |
SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies
Eight structures of human neutralizing antibodies that target the SARS-CoV-2 spike receptor-binding domain are reported and classified into four categories, suggesting combinations for clinical use.
- Christopher O. Barnes
- , Claudia A. Jette
- & Pamela J. Bjorkman
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Article |
Human germinal centres engage memory and naive B cells after influenza vaccination
The human germinal centre response to influenza virus vaccination is fuelled by the continued recruitment of naive B cells as well as pre-existing memory B cells.
- Jackson S. Turner
- , Julian Q. Zhou
- & Ali H. Ellebedy
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Perspective |
A perspective on potential antibody-dependent enhancement of SARS-CoV-2
The antibody-dependent enhancement of disease is reviewed, with an emphasis on implications for the prevention and treatment of SARS-CoV-2 infection.
- Ann M. Arvin
- , Katja Fink
- & Herbert W. Virgin
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Article |
Brain control of humoral immune responses amenable to behavioural modulation
Neuronal activities in the central amygdala and paraventricular nucleus are transmitted via the splenic nerve to increase plasma cell formation after immunization, and this process can be behaviourally enhanced in mice.
- Xu Zhang
- , Bo Lei
- & Hai Qi
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Article |
A GPR174–CCL21 module imparts sexual dimorphism to humoral immunity
Male and female B cells show differing abilities to localize and contribute to germinal centres, in a way that depends on the G-protein-coupled guidance receptor GPR174 and its chemokine ligand CCL21.
- Ruozhu Zhao
- , Xin Chen
- & Hai Qi
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Matters Arising |
Reply to: Do not discard Staphylococcus aureus WTA as a vaccine antigen
- David Gerlach
- , Yinglan Guo
- & Andreas Peschel
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Letter |
Migrant memory B cells secrete luminal antibody in the vagina
In a mouse model of herpes simplex 2 virus infection, circulating memory B cells—rather than plasma cells—are shown to be the source of antibody secretion in the vaginal lumen following secondary infection.
- Ji Eun Oh
- , Norifumi Iijima
- & Akiko Iwasaki
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Letter |
Commonality despite exceptional diversity in the baseline human antibody repertoire
A genetic study of the baseline human antibody repertoire, based on the circulating B cell populations of ten subjects, reveals universally shared antibody clonotypes within repertoires that are largely unique to the individual.
- Bryan Briney
- , Anne Inderbitzin
- & Dennis R. Burton
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Letter |
Tracing HIV-1 strains that imprint broadly neutralizing antibody responses
Similarity of antibody responses in HIV-1 transmission pairs reveals a significant impact of the virus genome on imprinting antibody responses.
- Roger D. Kouyos
- , Peter Rusert
- & Sabine Yerly
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Letter |
Public antibodies to malaria antigens generated by two LAIR1 insertion modalities
Up to 10% of individuals in malaria-endemic regions produce antibodies that react to malaria antigens through an additional LAIR1 domain that is inserted by two different insertion modalities.
- Kathrin Pieper
- , Joshua Tan
- & Antonio Lanzavecchia
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Article |
TFH-derived dopamine accelerates productive synapses in germinal centres
Human follicular helper T cells engaging in synaptic interactions with germinal centre B cells release dopamine stored in chromogranin B+ granules, causing rapid externalization of ICOS ligand, which in turn enhances CD40L delivery to the synaptic cleft and synaptic contact, and results in an accelerated response.
- Ilenia Papa
- , David Saliba
- & Carola G. Vinuesa
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Letter |
High-avidity IgA protects the intestine by enchaining growing bacteria
Oral-vaccine-induced IgA cross-links growing bacteria into clonal aggregates, inhibiting pathogenesis, adaption and the spread of antimicrobial resistance genes.
- Kathrin Moor
- , Médéric Diard
- & Emma Slack
