Biology subjects

Smerczynski, J.

Publications and source records attributed to Smerczynski, J..

3 recordsLinked to original sources

bioRxiv2026

Germinal center-independent memory B cells provide rapid protection from lethal influenza challenges

Memory B cell recall responses are crucial for rapid protection from pathogens expressing previously encountered antigens. While germinal centers (GCs) contribute to durable B cell memory in many contexts, GC formation is attenuated or completely abrogated during some severe infections. Whether GC-independent responses generate functional memory B cells that may contribute to protective immunity remains unclear. Using mice lacking GCs, we identified a durable class-switched GC-independent memory B cell population that was generated dominantly through a T-cell-dependent response. Vaccine-induced non-GC memory B cells demonstrated greater diversity and provided humoral protection from matched and diverse vaccine-unmatched influenza viral challenges. These results identify a unique, durable, diverse, GC-independent memory B cell population that can mediate rapid protection from severe infections by mutable pathogens.

immunology↗

bioRxiv2025

Constitutive NF-kB Activation is Amplified by VSV in Aggressive PC3 Prostate Cancer Cells that Resist Viral Oncolysis

Cancer cells often have defects in antiviral pathways, making them susceptible to oncolytic viruses like vesicular stomatitis virus (VSV). However, some cancer cells resist viral infection through the constitutive expression of interferon-stimulated genes. This study examined whether NF-{kappa}B activation and NF-{kappa}B-dependent antiviral signaling contributes to resistance to VSV infection in the PC3 cell line, derived from an aggressive metastatic prostate cancer (PrCa) tumor. We found that NF-{kappa}B localized to the nucleus in VSV-infected PC3 cells, but not in the VSV-susceptible LNCaP PrCa cell line. Analysis of the upstream NF-{kappa}B inhibitor I{kappa}B- revealed higher levels of both total and phosphorylated I{kappa}B- in PC3 cells compared to LNCaP cells, indicating constitutive activation of the NF-{kappa}B pathway via an I{kappa}B--dependent mechanism. Notably, VSV infection did not alter I{kappa}B- phosphorylation in PC3 cells, suggesting that VSV may amplify NF-{kappa}B signaling through an I{kappa}B--independent pathway. Furthermore, PC3 cells displayed elevated levels of the NF-{kappa}B p65 protein subunit compared to LNCaP cells, with its phosphorylated form significantly increased upon VSV infection. These results from phosphorylation assays confirm that multiple steps in the NF-{kappa}B pathway are differentially activated in PC3 and LNCaP cells. Additionally, the expression of several NF-{kappa}B-dependent cytokine and proinflammatory genes, including IL12 and IL6, were upregulated following VSV infection in PC3 cells, as compared to LNCaP cells. Blocking the NF-{kappa}B pathway using a pharmaceutical inhibitor resulted in increased PC3 cell death with VSV infection. Collectively, these findings suggest that enhanced NF-{kappa}B signaling may underlie the resistance of PC3 cells to VSV oncolysis, potentially offering new insights into therapeutic strategies targeting NF-{kappa}B in resistant prostate cancers.

cancer biology↗

bioRxiv2025

Mouse digit AAV gene delivery into fibroblasts regulates regenerative outcome

The distal mouse digit tip regenerates post-amputation, while the proximal digit undergoes fibrosis. This study presents a comparative single-cell RNA sequencing-based analysis of regenerating and non-regenerating digits to computationally identify fibroblast subpopulations and genes associated with fibrosis and regeneration. To test the sufficiency of newly identified candidate genes to alter wound healing outcomes, we developed a robust adeno-associated virus gene delivery technique for digit fibroblasts. We found that overexpression of candidate pro-fibrotic genes Pcolce2 or Prelp in the blastema modifies normal regeneration and overexpression of candidate pro-regenerative factors Ccl2 or Mest in the proximal digit significantly increases bone deposition. These data demonstrate that the computational analysis combined with the AAV delivery approach presented in this study provides a powerful framework for identifying the driving factors of fibrosis and regeneration in the mammalian digit.

molecular biology↗