MLL1 directs gut-associated antibody responses to helminth and bacterial infections DOI Creative Commons
Yan Zhang, Clarissa R. Chakma,

Alana Kirn

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 22, 2024

Soil-transmitted helminths are one of the most common infections across world, yet how to promote an effective humoral response is not well understood. To ensure response, molecular programs underpin specialization antibody effector subtype microenvironmental signals. Here, we identify methyltransferase mixed-lineage leukemia 1 (MLL1) as a key target IgA-driven responses. Mll1 was increased in germinal center (GC) B cells gut-associated lymphoid tissues, and absence MLL1 mature led significant reductions GCs, IgG1 IgE helminth Trichuris muris. Yet, worm expulsion occurred more rapidly Mll1f/fCd23cre/+ mice compared control first two weeks infection. Accelerated clearance correlated with significantly elevated IgA+ plasma (PC), serum IgA fecal mice. Stimulation vitro confirmed that Mll1-deficiency accelerated formation PC this effect cell-intrinsic. CCR9 identified MLL1-regulated molecule by RNA-sequencing flow cytometry. Correspondingly, infected either T. muris or bacterium C. rodentium IgA+CCR9+ localized large intestine. This tailoring cell IgA-secreting healthier microbiome mice, Thus, study reveals tailor responses infections, which may aid development mucosal vaccines new targeted treatments.

Language: Английский

Conversion of vaccines from low to high immunogenicity by antibodies with epitope complementarity DOI
Alexandra R Dvorscek, Craig I. McKenzie,

Vera C Stäheli

et al.

Immunity, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

8
The multi-organ landscape of B cells highlights dysregulated memory B cell responses in Crohn's disease DOI Creative Commons
Dianyu Chen,

Song Xu,

Shuyan Li

et al.

National Science Review, Journal Year: 2025, Volume and Issue: 12(4)

Published: Jan. 10, 2025

ABSTRACT Crohn's disease (CD) is a prevalent type of inflammatory bowel (IBD) with dysregulated antibody responses. However, there lack comprehensive analysis B cell responses in CD. Here, we collected cells from the small intestine, colon and blood CD patients control subjects. Through coupled transcriptome immunoglobulin (Ig) gene individual cells, characterized cellular composition, Ig clonotype different subtypes. We observed shared disruptions plasma (PC) between IBD revealed heterogeneity memory (MBCs) showed positive correlation gut resident-like MBCs severity. Furthermore, our demonstrated an increased direct differentiation into PCs patients. Overall, this study demonstrates significantly altered associated chronic inflammation during highlights potential role mucosal pathogenesis.

Language: Английский

Citations

0
Memory B cells and their transcriptomic profiles associated with belimumab resistance in systemic lupus erythematosus in the maintenance phase DOI Creative Commons
Takeshi Iwasaki, Hajime Yoshifuji, Koji Kitagori

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 5, 2025

The factors contributing to the treatment efficacy of belimumab in patients with systemic lupus erythematosus (SLE) maintenance phase are unknown. Here, we collected blood samples from SLE (n=44) treated before and three six months after treatment. RNA-Seq whole was performed, gene expression quantified. Immune cell type enrichment analysis estimated immune subtype proportions each subtype. Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) < 4 at set as primary criterion. Non-responders exhibited upregulated B proliferation signals treatment, associated an increased number memory cells. A higher proportion cells predicted poor response ( p =5.1×10 -4 ). This also changes disease activity glucocorticoid dose compared baseline. Belimumab did not affect during time course, contrast naïve Higher type-I interferon (IFN) scores lower white complement C4 levels. Transcriptomic non-responders revealed significant upregulation immunoglobulin genes (Ig). Memory high Ig them were identified a treatment-resistant factor patients. Lower counts may serve clinical markers

Language: Английский

Citations

0
EZH2 coordinates memory B-cell programming and recall responses DOI Open Access
Keenan J Wiggins, M. Williams,

Sakeenah L. Hicks

et al.

The Journal of Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Abstract Antigen-experienced memory B-cells (MBC) are endowed with enhanced functional properties compared to naïve B cells and play an important role in the humoral response. However, epigenetic enzymes programs that govern their rapid differentiation incompletely understood. Here, of histone H3 lysine 27 methyltransferase EZH2 formation MBC response influenza infection was determined Mus musculus. expressed all postactivated B-cell subsets, including antibody-secreting (ASC), maximal expression germinal center (GC) cells. Deletion resulted a skewing pool towards non-GC, IgM+ subset failed fully express CCR6 CD73 at both early late time points. Intriguingly, although protein levels were reduced knockout MBC, deletion not efficient, indicating strong selective pressure maintain activity. Single-cell RNA-seq antigen-specific identified core set upregulated genes likely targets across subsets. Finally, defects ability form secondary ASC GC lethal challenge observed EZH2-deficient mice, significant impairment absence EZH2. These data show is critical modulator potential during reactivation.

Language: Английский

Citations

0
Transcriptional Control of Interferon-Stimulated Genes DOI Creative Commons
Olga Babadei, Birgit Strobl, Mathias Müller

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 107771 - 107771

Published: Sept. 1, 2024

Language: Английский

Citations

3
Advances and challenges in investigating B-cells via single-cell transcriptomics DOI Creative Commons
Oliver P. Skinner,

Saba Asad,

Ashraful Haque

et al.

Current Opinion in Immunology, Journal Year: 2024, Volume and Issue: 88, P. 102443 - 102443

Published: June 1, 2024

Single-cell RNA sequencing (scRNAseq) and Variable, Diversity, Joining (VDJ) profiling have improved our understanding of B-cells. Recent scRNAseq-based approaches led to the discovery intermediate B-cell states, including preplasma cells pregerminal centre B-cells, as well unveiling protective roles for B-cells within tertiary lymphoid structures in respiratory infections cancers. These studies transcriptional epigenetic control development atypical memory differentiation. Advancements temporal parallel with transcriptomic VDJ consolidated trajectory clones over course infection vaccination. Challenges remain studying states across tissues humans, relating spatial location phenotype function, examining antibody isotype switching events, unequivocal determination clonal relationships. Nevertheless, ongoing multiomic assessments cellular interactions promise new avenues improving humoral immunity combatting autoimmune conditions.

Language: Английский

Citations

1
mRNA Vaccines Against COVID-19 as Trailblazers for Other Human Infectious Diseases DOI Creative Commons
Rossella Brandi, Alessia Paganelli, Raffaele D’Amelio

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(12), P. 1418 - 1418

Published: Dec. 16, 2024

mRNA vaccines represent a milestone in the history of vaccinology, because they are safe, very effective, quick and cost-effective to produce, easy adapt should antigen vary, able induce humoral cellular immunity. Methods: To date, only two COVID-19 one RSV have been approved. However, several currently under development for prevention human viral (influenza, immunodeficiency virus [HIV], Epstein–Barr virus, cytomegalovirus, Zika, respiratory syncytial metapneumovirus/parainfluenza 3, Chikungunya, Nipah, rabies, varicella zoster herpes simplex 1 2), bacterial (tuberculosis), parasitic (malaria) diseases. Results: RNA viruses, such as severe acute syndrome coronavirus (SARS-CoV)-2, HIV, influenza, characterized by high variability, thus creating need rapidly circulating strain, task that can easily accomplish; however, speed variability may be higher than time needed vaccine adapted. vaccines, using lipid nanoparticles delivery system, act adjuvants, powerfully stimulating innate well adaptive immunity, both humoral, which is waning, cell-mediated, highly persistent. Safety profiles were satisfactory, considering slight increase prognostically favorable anaphylactic reactions young females myopericarditis males has observed. Conclusions: The pandemic determined shift use RNA: after having used medicine micro-RNAs tumor new era anti-infectious begun, great development, either improve already available, but unsatisfactory, or develop protective against infectious agents no preventative tools realized yet.

Language: Английский

Citations

1
Everlasting first impressions in B cells DOI
Soyeon Kim, Jonathan S. Maltzman

Science Immunology, Journal Year: 2024, Volume and Issue: 9(95)

Published: May 3, 2024

Initial imprinting by type 1 interferons shapes memory B cell generation in chronic viral infection.

Language: Английский

Citations

0
Detection of Lymphocytic Choriomeningitis Virus-Specific Memory B Cells Using Antigen Tetramers DOI
Lucy Cooper, Christopher Szeto,

Dhilshan Jayasinghe

et al.

Methods in molecular biology, Journal Year: 2024, Volume and Issue: unknown, P. 117 - 129

Published: Jan. 1, 2024

Language: Английский

Citations

0
Polarization of the memory B cell response DOI

Lizzette Pérez-Pérez,

Brian J. Laidlaw

Journal of Leukocyte Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 14, 2024

Abstract Memory B cells are long-lived that induced following infection or vaccination. Upon antigen re-encounter, memory rapidly differentiate into antibody-secreting germinal center cells. While an important component of long-term protective immunity vaccination, they also contribute to the progression diseases such as autoimmunity and allergy. Numerous subsets have been identified in mice humans possess phenotypic functional differences. Here, we review transcriptional circuitry governing B-cell differentiation function. We then summarize emerging evidence inflammatory environment which develop has role shaping their phenotype examine pathways regulating development during a type 1-skewed 2-skewed immune response.

Language: Английский

Citations

0