B cells are an indispensable component of the adaptive immune system, essential for effective protection against pathogens. B cells rely on B cell receptor (BCR) to interact with antigens and to trigger various biological processes and signaling pathways. Defects in BCR signaling can lead to diseases such as immunodeficiency, cancer, and autoimmune disorders. While the roles of BCR signaling in antigen processing, internalization, and presentation, antibody production and B cell survival are well documented, the mechanisms by which BCR activation controls these multiple biological processes remain poorly understood. In this study, we employed three distinct approaches to gain unprecedented insight into the identity, dynamics and environment of BCR signaling proteins, as well as the multifaceted biological processes or pathways that are concomitantly activated in response to BCR stimulation. Firstly, we utilized proximity biotinylation by ascorbate peroxidase 2 (APEX2) to obtain high-coverage mass spectrometric data on the identity and dynamics of proteins in the vicinity of the BCR upon activation. This method leverages the efficient promiscuous biotinylation activity of the APEX2 enzyme, which enables kinetic assessment of the local proteome with high spatiotemporal resolution, within approximately 20 nm and a 1-min time window. Secondly, we developed a new in silico pipeline, AutoCoEV, for analyzing large protein datasets and to predict inter-protein co-evolution. This pipeline was piloted to explore potential functional interactions or co-dependencies among selected lipid raft resident proteins identified in the APEX2 study. Lastly, we developed a methodology to achieve a comprehensive overview of the proteome at the immunological synapse (IS) in primary mouse B cells. This technique uses magnetic beads to emulate antigen-presenting cells, which initiated the formation of the IS, allowing efficient isolation of bead-associated cell adhesions. The results presented in this thesis provide a valuable reference for the early proteomic events following BCR activation, enhancing our understanding of the complex signaling mechanisms that govern B cell function.