L2pB1 cells are a subset of B-1 B lymphocytes expressing programmed death ligand 2 (PD-L2) on their surface. They constitute 30-50% of B lymphocytes in the mouse peritoneal cavity and contribute to the production of natural IgM antibody. Previous studies have indicated a protective role of B-1 B cells in attenuating atherosclerosis and insulin resistance. We report that L2pB1 cells possess a unique IgM antibody specificity for phosphorylcholine (PC) and phosphatidylcholine (PtC) IgM enabling them to perform PC- and PtC-specific phagocytosis of PtC-nanoparticles. Here we demonstrate that induced depletion of L2pB1 in a transgenic mouse model with L2pB1-specific diphtheria toxin receptor (DTR) expression increases abdominal inflammation in the peritoneal cavity as well as the visceral adipose tissue in diet-induced obese (DIO) mice. L2pB1-depleted DIO mice also display increased triglycerides and blood glucose levels per gram of body weight relative to PBS-injected control DIO mice. Our results suggest that L2pB1 cells may play a role in anti-inflammatory regulation in DIO. Further investigation is required to discover how L2pB1 cells protect from obesity-induced inflammation and whether L2pB1 cells can provide cellular therapy to control chronic inflammation in obese patients. / 2018-06-16T00:00:00Z

INTRODUCTION: Programmed Death Ligand 2 positive B1 cells (L2pB1) cells have a unique immunoglobulin repertoire that is poly-reactive to self-antigens and have previously been shown to have an essential role in autoimmunity. The active accumulation of L2pB1 cells inside tumors grown in vivo led us to hypothesize that this subpopulation of B1a cells may play a role in the immunosurveillance of cancer. Here, we report our investigation of the role of L2pB1 cells in the antitumor response using a three dimensional (3D) murine melanoma and colon cancer models. Our results showed that the depletion of L2pB1 cells rendered the loss of tumor inhibition effects of the syngeneic peritoneal immune cells. METHODS: Lymphocytes were collected from L2pB1 cell depleted and non-depleted peritoneal cavity washout (PCW) from an inducible knockout mouse model. Then tumor spheroids were incubated with PCW cells. Spheroid cross-sectional area (CSA) and volume were measured using a Celigo plate imager and Keyence fluorescence microscope. RESULTS: Tumor spheroid growth was significantly inhibited following incubation with syngeneic PCW but not with splenocytes. Depletion of L2pB1 significantly attenuated the tumor-inhibition effect and showed a negligible difference from the untreated control. This loss of tumor inhibition indicated that L2pB1 cells are essential for the tumor-inhibition effects of autologous peritoneal immune cells. CONCLUSIONS: These findings demonstrate the robust anti-tumor function of L2pB1 cells. In particular, peritoneal L2pB1 cells play an essential role in cancer inhibition. Future studies into the activation and antigen presentation pathways of L2pB1 cells could lead to novel immunotherapy of cancer.