TIM-4 Identifies Effector B Cells Expressing a RORγt-Driven Proinflammatory Cytokine Module That Promotes Immune...

Area of Science:

• Immunology
• Cell Biology

Background:

• B cells are known to produce pro-inflammatory cytokines, contributing to diverse immune responses.
• The specific subset of B cells and their associated cytokine profiles in inflammation are not fully elucidated.

Purpose of the Study:

• To identify and characterize a novel subset of pro-inflammatory B cells.
• To investigate the role of the phosphatidylserine receptor TIM-4 in B cell effector function.

Main Methods:

• Flow cytometry and cytokine analysis to identify TIM-4+ B cells and their cytokine production.
• In vivo studies using experimental autoimmune encephalomyelitis (EAE) models and allograft rejection models.
• Analysis of signaling pathways including IL-23R and transcription factors like RORγt.

Main Results:

• TIM-4+ B cells were found to preferentially express IL-17A, IL-22, IL-6, IL-1β, and GM-CSF.
• This pro-inflammatory cytokine expression is dependent on IL-23R signaling and RORγt.
• IL-17A produced by TIM-4+ B cells exacerbates EAE and allograft rejection and inhibits regulatory B cell differentiation.

Conclusions:

• TIM-4 identifies a subset of RORγt+ effector B cells (Beff) with a pro-inflammatory profile.
• TIM-4+ B cell-derived IL-17A promotes inflammation and enforces effector B cell function.
• TIM-4 serves as a valuable marker for studying Beff differentiation and function.