P75(NTR) activation limits CD21(lo) B cell subsets expansion in response to autoimmune-inducing challenges.

Studies, including our own, suggest that p75(NTR) plays a pivotal role in immune regulation. Here, we aimed to uncover the role of p75(NTR) signaling in regulating CD21(lo) B cell subsets, which are known to facilitate autoimmune activity, and to identify possible regulatory transcripts involved. Through in vitro assays, in vivo models, and RNA-seq analysis, we found that p75(NTR) expression and CD21(lo) B cell expansion were increased in B cells following TLR7/9 stimulation in vitro and in pristane-challenged mice in vivo. Interestingly, p75(NTR) deficiency led to a further expansion of CD21(lo) B cells and enhanced their pro-inflammatory characteristics. RNA-seq data revealed notable transcript alterations associated with CD21(lo) B cells, including increased Tbx21 expression. A potential role for p75(NTR) downstream signaling via phosphorylated p65 (p-p65) was also proposed. Our study provides insights into the role of p75(NTR) in restraining the development of CD21(lo) subsets and modulating autoimmune activity in response to autoimmune challenges.