Inducible IL-12-producing B cells regulate Th2-mediated intestinal inflammation

Area of Science:

• Immunology
• Gastroenterology

Background:

• A previously identified B-cell subset in T-cell receptor alpha knockout (TCRalphaKO) mice produces IL-10 and attenuates colitis.
• The precise mechanism by which these IL-10-producing B cells regulate inflammation remains unclear.

Purpose of the Study:

• To investigate the role of IL-10-producing B cells in regulating intestinal inflammation in TCRalphaKO mice.
• To determine if IL-10-producing B cells directly or indirectly modulate inflammatory responses.

Main Methods:

• Flow cytometry, ELISA, quantitative PCR, and RNase protection assays were used to analyze cytokine production in mesenteric lymph node (MLN) B cells.
• IL-12p35-deficient TCRalpha double knockout mice were generated to study the function of IL-12p70 in colitis pathogenesis.

Main Results:

• IL-12p35 expression in MLN B cells was dependent on the presence of IL-10 and B cells.
• Transfer of IL-10-producing B cells restored IL-12p35 expression in B-cell-deficient mice.
• IL-12p35-deficient mice exhibited more severe colitis, indicating IL-12's role in regulating Th2-mediated inflammation.
• MLN B cells from TCRalphaKO mice, but not IL-12p35-deficient mice, suppressed colitis upon transfer.

Conclusions:

• A novel subset of regulatory B cells producing IL-12 has been identified.
• These IL-12-producing regulatory B cells develop under Th2-mediated intestinal inflammation and require IL-10.
• This B-cell subset plays a crucial role in regulating intestinal inflammation.