Get started
Work

Unraveling the distinct roles of the MyD88 and TRIF signaling pathways in B cell activation and differentiation 3236

Year: 2025
Type: article
Abstract: Description B cells activation occurs via two primary mechanisms: engagement of the B cell receptor (BCR) with antigens and recognition of microbes via toll-like receptors (TLRs). Within TLR signaling, MyD88 and TRIF serve as key adaptor proteins. Among the TLRs expressed by B cells, TLR3 and TLR9 exclusively utilize the TRIF and MyD88 pathways, respectively, while TLR4 engages both pathways. This diversity makes these TLRs valuable tools for dissecting the roles of MyD88 and TRIF pathways in B cell function. Here, we stimulated B cells through TLR3, -4, and -9, both individually and in various combinations, with or without BCR stimulation, to explore their synergistic and antagonistic interactions. Our findings reveal that TRIF pathway promotes Type I interferons, enhancing the expression of costimulatory molecules like CD86. In contrast, MyD88 signaling suppresses costimulatory molecules and antigen presentation, while promoting metabolic activation, B cell proliferation, antibody production, and the secretion of proinflammatory cytokines. Using B cells from MyD88- or TRIF-deficient mice, we demonstrated that crosstalk between these pathways is limited. Notably, MyD88 signaling exerts a permissive effect on TLR4 responses, while TRIF determines their magnitude. Lastly, RNA-seq analyses of TLR4-stimulated B cells from WT, TRIF KO, MyD88 KO, or double KO mice revealed distinct genetic programming. Altogether, our results provide new insights into the dynamics of TLR signaling in B cells. Funding Sources NIH/ NIGMS R35 GM155038, Pelotonia Institute of Immunoonclology funds Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)
DOI: 10.1093/jimmun/vkaf283.1056
Language: English
Subfield: Immunology
Open Access status: bronze
OpenAlex ID: W4416448631
FWCI:
Cites:
Cited by:
Related to: