Bacterially activated B-cells drive T cell differentiation towards Tr1 through PD-1/PD-L1 expression

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Regulatory B cells (Bregs) are crucial for immune tolerance, producing IL-10 in various diseases.
• The function of Bregs in Helicobacter infections remains largely unexplored.
• Helicobacter felis infection serves as a model to investigate Breg phenotypes and functions.

Purpose of the Study:

• To elucidate the phenotype and function of Helicobacter-stimulated B cells.
• To identify the mechanisms by which Bregs influence T cell differentiation in the context of H. felis infection.
• To explore the role of PD-1/PD-L1 and TGF-β in Breg-mediated immune responses.

Main Methods:

• Phenotypic analysis of Helicobacter felis-stimulated B cells.
• Assessment of cytokine production (IL-10, TGF-β, IL-6, TNF-α) by B cell subsets.
• Investigation of T cell differentiation (Tr1 and Th17 cells) induced by B cells.
• Flow cytometry to identify cell surface markers (CD9, Tim-1, PD-1, PD-L1, CD49b, LAG-3).

Main Results:

• Helicobacter felis-stimulated IL-10-producing B cells (Hf_stim- IL-10⁺ B) comprise B10 and T2-MZP cells expressing CD9, Tim-1, and PD-1.
• Helicobacter felis-stimulated IL-10-nonproducing B cells (Hf_stim- IL-10^- B) are primarily MZ B cells expressing PD-L1 and secreting TGF-β, IL-6, and TNF-α.
• Both Hf_stim- IL-10⁺ B and Hf_stim- IL-10^- B cells induce CD49b⁺LAG-3⁺ Tr1 cells.
• Hf_stim- IL-10^- B cells induce Th17 cell differentiation dependent on TGF-β.
• A novel PD-1/PD-L1-driven mechanism for B cell-dependent Tr1 cell differentiation was identified.

Conclusions:

• Helicobacter felis-stimulated B cells induce Tr1 cells via the PD-1/PD-L1 axis.
• Helicobacter felis-stimulated B cells induce Th17 cells through TGF-β secretion.
• This study reveals novel mechanisms of Breg function in Helicobacter infection, impacting immunological tolerance.