This chapter provides insights into the early activation events of B cells in response to antigenic stimulation, the adaptive immune response of B cells that begins with the B cell receptors (BCRs) to specific antigens on their surfaces, the organization and dynamics of the BCRs in the unstimulated or “resting” state, and how these findings relate to current models of BCR activation. It is shown that when the BCR recognizes and binds antigen, it initiates a series of intracellular signaling events that lead to B cell activation and immune responses. In addition, this chapter explores BCR microcluster formation and B cell activation, as well as the role of the coreceptor CD19 in BCR microcluster recruitment and downstream signaling. CD19 acts as a B cell–specific coreceptor that enhances BCR signaling. Finally, this chapter highlights the role of B cell contraction in B cell activation and immune synapse formation, a process that is dependent on actin dynamics, and positively correlates with antigen-induced signal strength. With these findings, this chapter provides new insights into understanding how B cells respond to specific threats while minimizing responses to self-antigens or nonspecific molecules.