The chapter provides an in-depth analysis of the B cell receptor (BCR), a critical immunoglobulin molecule on B lymphocytes that significantly influences B cell survival, development, and activation. It begins by detailing the composition and structure of the BCR, highlighting the diversity of the variable (V) and constant (C) regions of both heavy and light chains, as well as complementarity determining regions (CDRs) that determine antigen specificity. The chapter then delves into the regulatory function of the BCR in the survival and development of naïve B cells and describes the initiation of B cell activation following BCR-antigen binding. Two predominant models of BCR activation, the conformational change model and the kinetic segregation model, are introduced, along with a focus on BCR microclusters and the recruitment of the coreceptor CD19, which is instrumental in triggering downstream signaling pathways. The chapter culminates by underscoring the cytoskeleton reorganization’s role in B cell spreading, a process vital for B cell function and regulation. Collectively, these insights lay the groundwork for a more profound comprehension of B cell biology and offer potential targets for future immunotherapeutic strategies. This chapter is essential for advancing our understanding of the molecular underpinnings of B cell–mediated immunity and its implications for disease pathogenesis and treatment.