Agolini, E. | bioRxiv Science

bioRxiv2026

Systemic-to-mucosal trafficking of memory B cells contributes to humoral immunity in the upper respiratory tract

Systemic vaccination induces serum antibodies and circulating memory B cells, protects from severe disease, but does not ensure sterilizing immunity in the upper respiratory tract, where many respiratory pathogens initiate infection. How systemic memory B cells contribute to mucosal immunity remains unclear. Using multiparametric flow cytometry, single-cell RNA and V(D)J sequencing, and functional analyses of paired blood and nasal/oropharyngeal samples, we characterized human B cells across systemic and mucosal compartments. Swab-derived B cells transcriptionally overlap with circulating activated memory B cells while exhibiting distinct features of activation, tissue retention, and spontaneous IgA/IgG secretion. Approximately 6% of mucosal B-cell clones were shared with blood, indicating systemic-mucosal connectivity. Both infection and vaccination expanded two circulating antigen-specific activated memory B cells subsets, whereas antigen-specific B cells accumulated in the upper respiratory tract only following local inflammation. The finding that B-cell recruitment is reactive rather than preemptive may explain the limited efficacy of parenteral vaccines and provides a rationale for developing integrated systemic-mucosal vaccination strategies.

immunology↗

bioRxiv2020

Episignatures stratifying ADNP syndrome show modest correlation with phenotype

ADNP syndrome, also known as Helsmoortel-van Der Aa syndrome, is a neurodevelopmental condition associated with intellectual disability/developmental delay, autism spectrum disorder, and multiple medical comorbidities. ADNP syndrome is caused by mutations in the activity-dependent neuroprotective protein (ADNP). A recent study identified genome-wide DNA methylation changes in 22 individuals with ADNP syndrome, adding to the group of neurodevelopmental disorders with an epigenetic signature. This methylation signature segregated those with ADNP syndrome into two groups, based on the location of the mutations. Here, we conducted an independent study on 24 individuals with ADNP syndrome and replicated the existence of the two, mutation-dependent ADNP episignatures. To probe whether the two distinct episignatures correlate with clinical outcomes, we used deep behavioral and neurobiological data from two prospective cohorts of individuals with a genetic diagnosis of ADNP syndrome. We found limited phenotypic differences between the two ADNP groups, and no evidence that individuals with more widespread methylation changes are more severely affected. Also, in spite of the methylation changes, we observed no profound alterations in the blood transcriptome of individuals with ADNP syndrome. Our data warrant caution in harnessing methylation signatures in ADNP syndrome as a tool for clinical stratification, at least with regards to behavioral phenotypes.

developmental biology↗