# P75NTR activation limits CD21lo B cell subsets expansion in response to autoimmune-inducing challenges

## TL;DR

This study shows that P75NTR limits the growth of a specific B cell type linked to autoimmunity when the immune system is challenged.

## Contribution

The novel finding is that P75NTR restrains CD21lo B cell expansion and modulates autoimmune activity via p-p65 signaling.

## Key findings

- P75NTR expression increases in B cells after TLR7/9 stimulation.
- P75NTR deficiency leads to greater CD21lo B cell expansion and pro-inflammatory traits.
- RNA-seq reveals Tbx21 upregulation and potential p-p65 signaling involvement in P75NTR function.

## Abstract

Studies, including our own, suggest that p75NTR plays a pivotal role in immune regulation. Here, we aimed to uncover the role of p75NTR signaling in regulating CD21lo 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 p75NTR expression and CD21lo B cell expansion were increased in B cells following TLR7/9 stimulation in vitro and in pristane-challenged mice in vivo. Interestingly, p75NTR deficiency led to a further expansion of CD21lo B cells and enhanced their pro-inflammatory characteristics. RNA-seq data revealed notable transcript alterations associated with CD21lo B cells, including increased Tbx21 expression. A potential role for p75NTR downstream signaling via phosphorylated p65 (p-p65) was also proposed. Our study provides insights into the role of p75NTR in restraining the development of CD21lo subsets and modulating autoimmune activity in response to autoimmune challenges.

•P75NTR expression increased in B cells following TLR7/9 stimulation•CD21lo B cells expand with increased activity after TLR7/9 stimulation•p75NTR loss enhances TLR7/9-induced expansion of CD21lo B cells•p75NTR may restrain CD21lo B cells via downstream p-p65 signaling

P75NTR expression increased in B cells following TLR7/9 stimulation

CD21lo B cells expand with increased activity after TLR7/9 stimulation

p75NTR loss enhances TLR7/9-induced expansion of CD21lo B cells

p75NTR may restrain CD21lo B cells via downstream p-p65 signaling

Immunology; Molecular biology; Cell biology