Biology subjects

Gregoire, C.

Publications and source records attributed to Gregoire, C..

4 recordsLinked to original sources

bioRxiv2025

Access to germinal center IL-4 microniches drives tissue-divergence of IgE memoryresponses

Immunoglobulin E (IgE) drives allergic disease, yet how memory B cells (MBCs) reactivate to produce IgE, and how tissue localization shapes recall responses, remains unclear. Using mouse models of airborne exposure to house dust mites and Alternaria, we found that allergen sensitization generates lymphoid- and lung-resident MBCs. Upon allergen re-exposure, these populations followed distinct differentiation trajectories: lymph node MBCs engaged a germinal center (GC)-dependent pathway that generated both IgG1 and IgE plasma cells (PCs), whereas lung MBCs followed a GC-independent route producing mainly IgG1 PCs. GC re-entry granted MBCs access to an IL-4-rich microniche formed by Tfh cells, which was essential for IgE production. Disrupting GC re-entry, IL-4 signaling, or Tfh-derived IL-4 during recall markedly reduced allergen-specific IgE titers. These findings reveal a spatially and cytokine-restricted mechanism that confines IgE memory to lymphoid organs, positioning GC IL-4 microniches as anatomical safeguards against IgE production at barrier sites frequently exposed to environmental antigens.

immunology↗

bioRxiv2025

Mucosal B cell memory selection integrates tissue-specific microbial cues via the IgA BCR

B cells engender plasma cells (PCs) and memory B cells (MBCs) to combat recurrent pathogens. While B cell receptor (BCR) affinity dictates fate decisions in clonally-restricted set-ups, the driving factors in more complex systems remain unknown. Here, we show that memory selection during mucosal infection is imprinted by inherent cues from barrier tissues: lungs skew selection towards MBCs while the gut favors PC entry, even in response to the same pathogen. This divergence is linked to differential BCR isotype usage across barrier tissues rather than to affinity. In the gut, the commensal-induced TGF-{beta}-rich milieu promotes B cell class-switching to IgA. Consequently, the IgA BCR bias selection towards PCs, a process that is counteracted by its cytosolic tail domain. Overall, mucosal B cell selection integrates tissue-specific cues by strongly relying on BCR isotype usage rather than affinity, with implications for nasal and oral vaccine development. One sentence summaryDivergent B cell memory strategies evolved in lung and gut mucosa to counteract recurrent pathogens.

immunology↗

bioRxiv2024

Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections

Plasmacytoid dendritic cells (pDCs) are major producers of type I/III interferons. As interferons are crucial for antiviral defense, pDCs are assumed to play an essential role in this process. However, robust evidence supporting this dogma is scarce. Genetic or pharmacological manipulations that eliminate pDC or disrupt their interferon production often affect other cells, confounding interpretation. To overcome this issue, we engineered pDC-less mice that are specifically and constitutively devoid of pDCs by expressing diphtheria toxin under coordinated control of the Siglech and Pacsin1 genes, uniquely co-expressed in pDCs. pDC-less mice mounted protective immunity against systemic infection with mouse Cytomegalovirus and showed higher survival and less lung immunopathology to intranasal infection with influenza virus and SARS-CoV2. Thus, contrary to the prevailing dogma, we revealed that pDCs and their interferons are dispensable or deleterious during several viral infections. pDC-less mice will enable rigorously reassessing the roles of pDCs in health and disease.

immunology↗

bioRxiv2021

Viral infection engenders bona fide and bystander lung memory B cell subsets through permissive selection

Lung-resident memory B cells (MBCs) provide localized protection against reinfection in the respiratory airways. Currently, the biology of these cells remains largely unexplored. Here, we combined influenza and SARS-CoV-2 infection with fluorescent-reporter mice to identify MBCs regardless of antigen specificity. scRNA-seq analysis and confocal imaging revealed that two main transcriptionally distinct subsets of MBCs colonize the lung peribronchial niche after infection. These subsets arise from different progenitors and are both class-switched, somatically mutated and intrinsically biased in their differentiation fate towards plasma cells. Combined analysis of antigen-specificity and B cell receptor repertoire unveiled a highly permissive selection process that segregates these subsets into "bona fide" virus-specific MBCs and "bystander" MBCs with no apparent specificity for eliciting viruses. Thus, diverse transcriptional programs in MBCs are not linked to specific effector fates but rather to divergent strategies of the immune system to simultaneously provide rapid protection from reinfection while diversifying the initial B cell repertoire.

immunology↗