Activation of p75NTR in B cells contributes to restraining the subset of CD21lo subsets against autoimmune-inducing challenges.

Objectives CD21 is a B cell surface protein that is essential for B cell activation and regulation. Recent evidence suggests that p75NTR is involved in the functional regulation of peripheral immune cells, including B cells. This study aimed to investigate the role of p75NTR signaling in regulating CD21lo B cell subsets and its role in disease conditions.Methods A combination of in vitro assays and in vivo models to assess the expression of p75NTR and CD21 on activated B cells. Additionally, transgenic mice were used to further investigate the effect of p75NTR deletion on CD21lo B cells. Splenic B cells were subjected to RNA sequencing (RNA- seq) analysis to identify transcriptomic alterations.Results Upregulation of p75NTR in B cells inhibited the expansion of CD21lo B cell subsets in splenic B cells following TLR stimulation in vitro and in mice challenged with pristane. p75NTR deficiency led to the expansion of CD21lo B cells and enhanced their proinflammatory characteristics. Additionally, our results suggest that phosphorylated p65 (p-p65) may contribute to the p75NTR-mediated expansion of CD21lo B cell subsets during TLR-mediated immune challenges.Conclusion Our study provides evidence that p75NTR expression in B cells is essential for limiting the expansion of CD21lo B cell subsets in autoimmune settings. This regulation is associated with hyperactivation of these cells and significant transcriptomic alterations, providing new insights into the molecular mechanisms by which p75NTR governs B cell development amid immune dysregulation.