B lymphocytes ameliorate Alzheimer?s disease-like neuropathology via interleukin-35

Increasing evidence supports the involvement of the peripheral immune system in the pathogenesis of Alz-heimer's disease (AD). In the present study, we found that B lymphocytes could mitigate beta-Amyloid (A beta) pathology and memory impairments in a transgenic AD mouse model. Specifically, in young 5 x FAD mice, we evidenced increased B cells in the frontal cortex and meningeal tissues; depletion of mature B cells aggravated these mice's A beta load and memory deficits. The increased B cells produced more interleukin-35 (IL-35) in the front cortex. We further found IL-35 neutralization exacerbated A beta pathology, while injecting IL-35 mitigated A beta load and cognitive dysfunction in 5 x FAD mice with or without mature B cell deficiency. Mechanistically, IL-35 inhibited neuronal BACE1 transcription through modulating the SOCS1/STAT1 pathway, and reduced A beta pro-duction accordingly. Reanalysis of the single-cell RNA sequencing data from blood samples of AD patients suggested an increased population of IL-35-producing B cells. Together, the present study revealed a novel effect of B lymphocyte-derived IL-35 on inhibiting A beta production in the frontal cortex, which may serve as a potential target for future AD treatment.

Automated summary

This study found that B lymphocytes could alleviate beta-Amyloid (Aβ) pathology and memory impairments in a transgenic AD mouse model. The depletion of mature B cells aggravated Aβ load and memory deficits in the mice.