Therapies, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 15, 2025
ABSTRACT Antibody production is central to protection against new pathogens and cancers, as well certain forms of autoimmunity. Antibodies often originate in the lymph node (LN), specifically at extrafollicular border B cell follicles, where T lymphocytes physically interact drive maturation into antibody-secreting plasmablasts. In vitro models this process are sorely needed predict aspects human immune response. Microphysiological systems (MPSs) offer opportunity approximate lymphoid environment, but so far have focused primarily on memory recall responses antigens previously encountered by donor cells. To date, no 3D culture system has replicated engagement between cells (T—B interaction) that leads antibody when starting with naïve Here, we developed a LN-MPS model early T—B interactions built from primary, encapsulated within collagen-based matrix. Within MPS, exhibited CCL21-dependent chemotaxis chemokinesis predicted. Naïve were successfully skewed chip an follicular helper (pre-Tfh) activated state, respectively, co-culture latter led CD38+ plasmablast dependent IgM. These required differentiation pre-Tfhs, physical cell-cell contact, sensitive ratio which pre-Tfh seeded on-chip. Dependence was greatest 1:5 T:B ratio, while proliferation signal 1:1 ratio. Furthermore, formation established We envision MPS primary lymphocyte physiology will enable mechanistic analyses humoral immunity vitro.
Language: Английский
Citations
0
Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: April 10, 2025
Lymphoid organ function depends on fibroblastic reticular cells (FRCs), the non-hematopoietic mesenchymal stromal that crucially support immune activity in human lymph nodes (LNs). The vitro study of immunology requires physiological LN models, yet inclusion FRCs current models is lacking. Here, we created an organotypic hydrogel model, containing native from tissue and ex vivo cultured autologous FRCs. During a oneweek culture period, enrichment into model benefited viability all cell populations, particularly B cells, promoted presence certain subsets including CD4+ naïve T unswitched (US) memory cells. enhanced production immune-related cytokines chemokines, such as activating factor TNF family (BAFF), CXC motif chemokine ligand 12 (CXCL12), CC 19 (CCL19) interleukin-6 (IL-6). Functionality was assessed through activation by CD3 stimulation or initiation allogenic reaction with different maturation statuses monocyte-derived dendritic (moDCs). Interestingly, expansion restricted FRC-enriched reflecting intrinsic characteristic As such, this highlights influence allows opportunity to further antigen-induced responses, e.g. vaccine immunotherapy testing.
Language: Английский
Citations
0
Bioprinting, Journal Year: 2024, Volume and Issue: 43, P. e00357 - e00357
Published: Sept. 13, 2024
Language: Английский
Citations
1
Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 1, 2024
Language: Английский
Citations
0
Toxicology Letters, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 1, 2024
Language: Английский
Citations
0
Therapies, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Citations
0
Therapies, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Citations
0