Intrinsic Properties of immunoglobulin IgG1 Isotype-Switched B Cell Receptors Promote Microclustering and the Initiation of Signaling

Abstract

Memory B cells express high-affinity, immunoglobulin GB cell receptors (IgG BCRs) that enhance B cell responses, giving rise to the rapid production of high-affinity, IgG antibodies. Despite the central role of IgG BCRs in memory responses, the mechanisms by which the IgG BCRs function to enhance B cell responses are not fully understood. Using high-resolution live-cell imaging, we showed that IgG1 BCRs dramatically enhanced the earliest BCR-intrinsic events that followed within seconds of B cells' encounter with membrane bound antigen, including BCR oligomerization and BCR microcluster growth, leading to Syk kinase recruitment and calcium responses. The enhancement of these early events was dependent on a membrane proximal region of the IgG1 cytoplasmic tail not previously appreciated to play a role in IgG1 BCR signaling. Thus, intrinsic properties of the IgG1 BCR enhance early antigen-driven events that ultimately translate into heightened signaling.