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CD40-induced humoral immunity

ABSTRACT: CD40CD40 induces a uniquely sustained NEMO modification and persistent RelA transcriptional activity to efficiently generate class-switched antibodies.

ORGANISM(S): Mus musculus

PROVIDER: GSE325803 | GEO | 2026/06/09

REPOSITORIES: GEO

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NEMO lysine mutant mice reveal ROS-RelA signaling required for optimal CD40-induced humoral immunity

Project description:Oxidative and genotoxic stresses activate NF-κB signaling through intracellular pathways distinct from those initiated by membrane receptors, but their physiological roles remain incompletely defined. We created the NEMODK mouse model with germline arginine substitutions at NEMO (NF-κB essential modulator) lysines 270 and 302, key sites for post-translational modifications selectively induced by these intracellular stresses to enable NF-κB signaling in vitro. NEMODK mice exhibited B cell-intrinsic defects in the generation of germinal center B cells and humoral responses. Mechanistically, NEMODK B cells displayed a CD40-specific NF-κB signaling defect, unrelated to acute canonical and delayed noncanonical NF-κB activity, which was accompanied by the lack of sustained NEMO monoubiquitination downstream of mitochondrial reactive oxygen species generation without relying on nuclear DNA damage. This specifically reduced persistent RelA activity and a failure to mount transcriptomic and epigenetic changes critical for homotypic B cell aggregation, cell proliferation, class switch recombination and antibody secreting cell generation. Thus, CD40 induces a uniquely sustained NEMO modification and persistent RelA transcriptional activity to efficiently generate class-switched antibodies.

2026-06-09 | GSE325910 | GEO

NEMO lysine mutant mice reveal ROS-RelA signaling required for optimal CD40-induced humoral immunity [NEMODK_CUTTAG]

2026-06-09 | GSE325580 | GEO

NEMO lysine mutant mice reveal ROS-RelA signaling required for optimal CD40-induced humoral immunity [NEMODK_ATACSeq]

2026-06-09 | GSE325579 | GEO

NEMO lysine mutant mice reveal ROS-RelA signaling required for optimal CD40-induced humoral immunity

Project description:NEMO lysine mutant mice reveal ROS-RelA signaling required for optimal CD40-induced humoral immunity

| PRJNA1442206 | ENA

NEMO lysine mutant mice reveal ROS-RelA signaling required for optimal CD40-induced humoral immunity [NEMODK_CUTTAG]

Project description:NEMO lysine mutant mice reveal ROS-RelA signaling required for optimal CD40-induced humoral immunity [NEMODK_CUTTAG]

| PRJNA1440503 | ENA

NEMO lysine mutant mice reveal ROS-RelA signaling required for optimal CD40-induced humoral immunity [NEMODK_ATACSeq]

Project description:NEMO lysine mutant mice reveal ROS-RelA signaling required for optimal CD40-induced humoral immunity [NEMODK_ATACSeq]

| PRJNA1440502 | ENA

CD40-induced humoral immunity

Project description:CD40-induced humoral immunity

| PRJNA1441975 | ENA

Venous plexus-associated lymphoid hubs support meningeal humoral immunity

Project description:There is increasing interest in how immune cells in the meninges, the membranes that surround the brain and spinal cord, contribute to homeostasis and disease in the central nervous system (CNS)1,2. The outer layer of meninges, the dura mater, has recently been described to contain both innate and adaptive immune cells, and function as a site for B cell development. Here, we identified organised lymphoid structures protecting fenestrated vasculature in the dura mater that we term dural-associated lymphoid tissue (DALT). We found the most elaborate immune organization, including lymphatic vessels, surrounding the rostral_x0002_rhinal confluence of sinuses. We termed this structure that interfaced with the skull bone marrow and a comparable venous plexus at the skull base, the rostral-rhinal venolymphatic hub. Immune aggregates were present in DALT during homeostasis and expanded with age or following challenge with systemic or nasal antigens. DALT contained germinal centre (GC) B cells, and supported the generation of somatically mutated, antibody-producing cells in response to a nasal pathogen challenge. Inhibition of lymphocyte entry into the rostral-rhinal hub at the time of nasal viral challenge abrogated the generation of germinal centre B cells and class-switched plasma cells, as did perturbation of B-T cell interactions. These data demonstrate lymphoid architecture around vasculature in dura mater that can sample antigens and rapidly support humoral immune responses following local pathogen challenge.

2024-03-04 | GSE254265 | GEO

CD40-independent help by memory CD4 T cells induces pathogenic alloantibody but does not lead to long-lasting humoral immunity.

Project description: Not available

| S-EPMC4019209 | biostudies-literature

Investigation of SARS-CoV-2 variants that escape from cellular immunity in the absence of humoral immunity

Project description:X-linked agammaglobulinemia (XLA) is a primary immunodeficiency causing a lack of immunoglobulin production. A COVID-19 patient with XLA showed persistent infection for more than 239 days, representing the longest duration yet reported, in whom SARS-CoV-2 evolved increased proliferative capacity. We identify a mutation of SARS-CoV-2 that is responsible for the immune escape from the cellular immunity of this patient, as well as the TCR that could recognize the wild type antigen but not the correspoinding mutant antigen.

2023-05-12 | GSE190895 | GEO

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