Biology subjects

Mathew, N. R.

Publications and source records attributed to Mathew, N. R..

3 recordsLinked to original sources

bioRxiv2025

Antibodies, Memory B Cells, and Antigen Valency Reshape B Cell Responses to Drifted Influenza Virus Vaccination

Antigenic drift in influenza A virus hemagglutinin (HA) limits humoral protective immunity. Here, we combine cell fate mapping with adoptive transfer of antigenic-site-specific antibodies (Abs) and memory B cells (MBCs) with moderately drifted HA vaccination in mice to better understand how this influences immune escape and protective responses. We demonstrate that drift in vaccine antigens affects MBC reactivation and naive B cell responses in germinal centers (GC). Strikingly, passively transferred monoclonal and polyclonal Abs suppress cognate epitope-specific GC B cell responses only when the vaccine antigen was multivalent while responses to monovalent recombinant trimeric HA remain unaffected. Using MBC and Abs co-transfer we unveil that antigenic site-specific suppression is more potent in blocking MBC rather than naive B cells entry into GC. In addition, we show that MBC hamper naive B cell recruitment to GC even in the absence of antibody transfer through local differentiation and Ab release in the responding lymph node. Altogether, our study reveals that serum Ab feedback depends on vaccine valency, while pre-existing MBC alone without Abs present can reshape immunodominance of naive B cells, with critical practical implications for rational universal influenza vaccine design.

immunology↗

bioRxiv2024

Nasal tissue-resident memory CD4+ T cells persist after influenza A virus infection and provide heterosubtypic protection

CD4 tissue-resident memory T cells (TRM) are crucial adaptive immune components involved in preventing influenza A virus (IAV) infection. Despite their importance, their physiological role in the upper respiratory tract, the first site of contact with IAV, remains unclear. Here, we find that, after IAV infection, antigen-specific CD4 TRM persist in the nasal tissue (NT) compartment after infection and provide protection upon heterosubtypic challenge. Single cell RNA sequencing analysis reveals that NT CD4 TRM are heterogeneous and transcriptionally distinct as compared to their lung counterparts. Mechanistically, we demonstrate that the CXCR6-CXCL16 axis promotes CD4 TRM residency in the NT. Furthermore, we show that the NT of mice and humans contains a high frequency of Th17 CD4 TRM that aid in local viral clearance and in reducing tissue damage. Collectively, our results support a robust physiological role for nasal tissue CD4 TRM in local protection during heterosubtypic IAV infection.

immunology↗

bioRxiv2020

Single cell BCR and transcriptome analysis after respiratory virus infection reveals spatiotemporal dynamics of antigen-specific B cell responses.

B cell responses are a critical component of anti-viral immunity. However, a comprehensive picture of antigen-specific B cell responses, differentiation, clonal proliferation and dynamics in different organs after infection is lacking. Here, we combined single-cell RNA sequencing with single-cell B cell receptor (BCR) characterization of antigen-specific cells in the draining lymph nodes, spleen and lungs after influenza infection. We identify several novel B cell subpopulations forming after infection and find organ-specific differences that persist over the course of the response. We discover important transcriptional differences between memory cells in lungs and lymphoid organs and describe organ-restricted clonal expansion. Strikingly, by combining BCR mutational analysis, monoclonal antibody expression and affinity measurements we find no differences between germinal center (GC)-derived memory and plasmacells, at odds with an affinity-based selection model. By linking antigen-recognition with transcriptional programming, clonal-proliferation and differentiation, these finding provide important advances in our understanding of antiviral B cell immunity.

immunology↗