The Regulatory Function of B Cells in Protection Against EAE by a Human Commensal Bacteria Polysaccharide (P05.111)

Abstract

Objective: To investigate the regulatory role of B cells in intestinal commensal Bacteroides fragilis polysaccharide A (PSA) protection of EAE. Background Intestinal commensal microbiota have the potential to modulate immune system against neuro-inflammation. Polysaccharide A (PSA), a zwitterionic capsular polysaccharide derived from the intestinal commensal Bacteroides fragilis and TLR2 agonist, is shown to protect mice against EAE via oral administration route. In this study, we will investigate the the regulatory function of B cells is one of the potential mechanisms underlying PSA protection against EAE. Design/Methods: CD19 + B cells from PSA or BPS orally administrated B6 donor mice were adoptively transferred to EAE-induced B6 recipient mice. Normal or TLR2 -/- CD19 + B cells were in vitro cultured with PSA for 72 hrs and supernatant IL-10 was measured by ELISA. IL-10-Thy1.1 (10BiT) reporter mice was induced with EAE and oral administrated of PSA or PBS as control. Cervical, mesenteric LNs and peyer9s patches were collected. Total CD19 + B cells and CD29 + CD19 + B cells were analyzed for their composition and IL-10 expression by FACS. Results: CD19 + B cells from PSA sensitized donors had stronger protective power against EAE than normal donors in a dosage-dependent manner. In vitro , PSA could stimulate CD19 + B cells production of IL-10 via TLR2 signaling. In vivo at early EAE development stage, PSA can tilt the composition of CD19 + B cells to CD5 + B1 phenotype and IL-10 expressive. Within the CD29 + CD19 + B cell niche, IL-10 + CD5 + B 1 cells are enriched. Conclusions: In MS/EAE, PSA tunes the CNS immuno-homeostasis via B cells. PSA could increase the IL-10 producing B1 subset. PSA enriches IL-10 + regulatory B cell type within brain homing niche, consistent with the reduction of neuro-inflammation by PSA treatment. TLR2 sensing of PSA both in vivo and in vitro is essential for the establishment of anti-inflammation function via PSA. Supported by: NIAID-AI061939 and CA1027A1/3-National Multiple Sclerosis Society. Disclosure: Dr. Wang has nothing to disclose. Dr. Telesford has nothing to disclose. Dr. Ochoa-Reparaz has nothing to disclose. Dr. Haque-Begum has received research support from Teva Neuroscience. Dr. Mielcarz has nothing to disclose. Dr. Kasper has nothing to disclose. Dr. Kasper has received personal compensation for activities with Teva Neuroscience, Serono, Inc., Bayer Pharmaceuticals Corporation, Genentech, Inc., Mederex as a consultant and participant on a scientifc advisory board. Dr. Kasper has received research support from Teva Neuroscience, Serono, Inc. and Bayer Pharmaceutical Corporation.