Background: Chemokine (C-C motif) receptor 2 (CCR2) contributes to autoimmune pathogenesis. However, the effect of CCR2 on B cell signaling and its role in autoimmunity remains unclear. Herein, we investigated the role of CCR2 in the B cell receptor (BCR) signaling pathway and aimed to illustrate its potential molecular mechanisms of action. Methods: To investigate the alterations in B cell signaling and the immune response, we used flow cytometry, western blotting, microscopic techniques, Seahorse assay, and immunofluorescence assay on samples from C57BL/6 mice and germinal CCR2-deletion mice. Results: The absence of CCR2 disturbed follicular B cell development. Furthermore, CCR2 absence was correlated with increased mTORC1-mediated energy metabolism and enhanced early B cell activation, which were induced by the up-regulation of BCR proximal signaling and F-actin accumulation. Mst1 and STAT1 were key factors in up-regulating the B cell activation in CCR2 deficient mice. The disrupted peripheral B cell differentiation and enhanced B cell signaling were associated with the inhibition mTORC1, Mst1, and STAT1. Moreover, loss of CCR2 caused a weakened T cell dependent antigen response, resulting in decreased antibody secreting cells and diminished antigen specific IgM levels. Conclusion: CCR2 is involved in the regulation of BCR signaling pathway by sequentially activating signaling pathways dominated by Mst1, mTORC1, and STAT1. Our study suggests that CCR2 might represent a novel therapeutic targeted for autoimmune diseases.