Temporally overlapping mechanisms diversify clonal B cell responsesin vivo DOI Creative Commons
Oliver P. Skinner,

Saba Asad,

Marcela L. Moreira

et al.

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

Published: Dec. 21, 2024

Abstract Single naive B cells amplify and diversify their responses when activated by cognate antigen, via Myc-dependent clonal expansion, immunoglobulin class switch recombination (CSR), phenotypic variation, somatic hypermutation (SHM). Whether these mechanisms act combinatorially in vivo to a single complex pathogen remains unclear. Since diversity the antigenic targets, functional classes, production kinetics of parasite-specific antibodies influences immunity malaria, we test here whether individual cell clones over time during Plasmodium infection treatment. During first week infection, amid widespread Type I Interferon (IFN)-mediated, bystander activation, CSR initiates soon after Myc up-regulation. then overlaps with resulting isotype variegation amongst certain clones. In second expanded seeding germinal centres (GC) both bifurcate into extra-follicular plasmablasts exhibit variegation, revealing substantial intra-clonal diversification. Over following month, GC undergo SHM at approximately four mutations per week, IgG mutational IgM + preserved GCs time. Anti-malarial intervention does not impede SHM, but instead exerts quantitative limits on size, plasma emergence circulating antibody titres. Finally, reveal contemporaneous developmental pathway that relocates from bone marrow spleen Thus, multiple temporally overlapping combine amplify, diversify, safeguard humoral immune responses. Graphical abstract Highlights Early temporal overlap expansion leads Clones variegation. accrue rates unaffected anti-malarials. triggers antigen-independent IFN-mediated activation. development is malaria shifting spleen.

Language: Английский

Metabolism and metabolites regulating hematopoiesis DOI
Baihao Zhang, Baihao Zhang

Current Opinion in Immunology, Journal Year: 2025, Volume and Issue: 93, P. 102525 - 102525

Published: Jan. 18, 2025

Language: Английский

Citations

0
MyD88 in osteoclast and osteoblast lineages differentially controls bone remodeling in homeostasis and malaria DOI Creative Commons
Jalal Alshaweesh, Rashmi Dash, Michelle Sue Jann Lee

et al.

International Immunology, Journal Year: 2024, Volume and Issue: 36(9), P. 451 - 464

Published: April 20, 2024

Chronic bone loss is an under-recognized complication of malaria, the underlying mechanism which remains incompletely understood. We have previously shown that persistent accumulation Plasmodium products in marrow leads to chronic inflammation osteoblast (OB) and osteoclast (OC) precursors causing through MyD88, adaptor molecule for diverse inflammatory signals. However, specific contribution MyD88 signaling OB or OC malaria-induced elusive. To assess direct cell-intrinsic role adult metabolism under physiological infection conditions, we used Lox-Cre system specifically deplete lineages. Mice lacking primarily maturing OBs showed a comparable decrease trabecular density by microcomputed tomography controls after yoelii non-lethal infection. In contrast, mice significantly less than controls, suggesting malaria-mediated mediators are controlled lineage. Surprisingly, however, depletion OB, but not OC, resulted reduced mass with decreased formation rates areas femurs conditions. Notably, insulin-like growth factor-1, key differentiation, was lower locally systemically when depleted OBs. Thus, our data demonstrate indispensable intrinsic differentiation formation, while lineages plays partial controlling following pathology. These findings may lead identification novel targets intervention pathologies, particularly malaria-endemic regions.

Language: Английский

Citations

0
The type 2 immune response in gut homeostasis and parasite transmission in malaria DOI
Nora Céspedes, Renée M. Tsolis, Adrian M. Piliponsky

et al.

Trends in Parasitology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

0
Temporally overlapping mechanisms diversify clonal B cell responsesin vivo DOI Creative Commons
Oliver P. Skinner,

Saba Asad,

Marcela L. Moreira

et al.

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

Published: Dec. 21, 2024

Abstract Single naive B cells amplify and diversify their responses when activated by cognate antigen, via Myc-dependent clonal expansion, immunoglobulin class switch recombination (CSR), phenotypic variation, somatic hypermutation (SHM). Whether these mechanisms act combinatorially in vivo to a single complex pathogen remains unclear. Since diversity the antigenic targets, functional classes, production kinetics of parasite-specific antibodies influences immunity malaria, we test here whether individual cell clones over time during Plasmodium infection treatment. During first week infection, amid widespread Type I Interferon (IFN)-mediated, bystander activation, CSR initiates soon after Myc up-regulation. then overlaps with resulting isotype variegation amongst certain clones. In second expanded seeding germinal centres (GC) both bifurcate into extra-follicular plasmablasts exhibit variegation, revealing substantial intra-clonal diversification. Over following month, GC undergo SHM at approximately four mutations per week, IgG mutational IgM + preserved GCs time. Anti-malarial intervention does not impede SHM, but instead exerts quantitative limits on size, plasma emergence circulating antibody titres. Finally, reveal contemporaneous developmental pathway that relocates from bone marrow spleen Thus, multiple temporally overlapping combine amplify, diversify, safeguard humoral immune responses. Graphical abstract Highlights Early temporal overlap expansion leads Clones variegation. accrue rates unaffected anti-malarials. triggers antigen-independent IFN-mediated activation. development is malaria shifting spleen.

Language: Английский

Citations

0