Biology subjects

Schapfl, M. A.

Publications and source records attributed to Schapfl, M. A..

2 recordsLinked to original sources

bioRxiv2026

Plasmalogen metabolism shapes germinal center immunity

Plasmalogens are membrane lipids whose roles in immunity are emerging through identification of the PEDS1 gene and advances in lipid analytics. Because PEDS1 catalyses the final step of plasmalogen biosynthesis, Peds1 knockout models plasmalogen loss. Building on reports of a haematopoietic phenotype in Peds1-deficient mice, we performed extended profiling to characterise haematological and immune phenotypes. In line with these previous investigations, mice showed reduced red blood cell counts and haematocrit, with increased mean platelet volume. At steady state, plasmalogen deficiency was associated with reduced germinal centre (GC) B cell frequencies in mucosal lymphoid tissues and lower basal serum IgG1 levels. Following immunisation, GC B cell frequencies and ovalbumin-specific IgG1 were similar across genotypes, yet GC B cells exhibited elevated mitochondrial superoxide and plasma cells displayed increased lipid peroxidation. To test for B cell-intrinsic effects, we used an in vitro GC culture, where Peds1-deficient B cells showed reduced class switching to IgG1, intracellular IgG1 accumulation and diminished IgG1 secretion. Together, these findings support a role for plasmalogens and PEDS1 as a lipid-metabolic modulator of GC dynamics and IgG1 output, consistent with broader ether lipid perturbations. Plasmalogen metabolism may therefore offer a potential entry point to modulate humoral immunity or haematopoiesis.

immunology↗

bioRxiv2024

Exact centriole counts are critical for B cell development but not function

Centrioles define centrosome structure and function. Deregulation of centriole numbers can cause developmental defects and foster malignant disease. The p53 tumor suppressor limits the growth of cells lacking or harboring additional centrioles and can be engaged by the "mitotic surveillance" or the "PIDDosome pathway", respectively. Here, we show that early B cell progenitors frequently present extra centrioles that are rapidly lost during maturation. Increasing centriole counts beyond physiological levels by Polo-like kinase 4 (PLK4) overexpression induces apoptosis, suggesting clearance of such cells during development. Remarkably, this apoptotic response is independent of PIDD1 or p53, but can be blocked by excess BCL2. In contrast, loss of centrosomes upon Plk4 deletion arrests B cell development at the pro B cell stage. This defect can be rescued by co-deletion of Usp28, a critical component of the mitotic surveillance pathway that restores cell number and function in the absence of centrioles. In both scenarios, too many and too few centrosomes, mitochondrial apoptosis is engaged to kill B cells with abnormal centriole counts during their development with progenitor B cells being intolerant to centriole loss but permissive to centriole amplification. Unexpectedly, our findings show that centrioles are dispensable for mounting an effective humoral immune response.

cell biology↗