RT Journal Article SR Electronic T1 Intrinsic properties of human germinal center B cells set antigen affinity thresholds JF Science Immunology JO Sci. Immunol. FD American Association for the Advancement of Science SP eaau6598 DO 10.1126/sciimmunol.aau6598 VO 3 IS 29 A1 Kwak, Kihyuck A1 Quizon, Nicolas A1 Sohn, Haewon A1 Saniee, Avva A1 Manzella-Lapeira, Javier A1 Holla, Prasida A1 Brzostowski, Joseph A1 Lu, Jinghua A1 Xie, HengYi A1 Xu, Chenguang A1 Spillane, Katelyn M. A1 Tolar, Pavel A1 Pierce, Susan K. YR 2018 UL http://immunology.sciencemag.org/content/3/29/eaau6598.abstract AB Germinal center (GC) B cells are essential to generating protective antibody responses and are selected through a process of affinity maturation. Kwak et al. now define intrinsic properties of human GC B cells that are critical to antigen affinity discrimination. They identified BCR-containing actin-rich pod-like structures that facilitated formation of highly stable synapses and antigen internalization but only when GC B cells engaged high-affinity antigens. These findings reveal the importance of these structures in setting thresholds for affinity selection and driving GC B cell responses.Protective antibody responses to vaccination or infection depend on affinity maturation, a process by which high-affinity germinal center (GC) B cells are selected on the basis of their ability to bind, gather, and present antigen to T follicular helper (Tfh) cells. Here, we show that human GC B cells have intrinsically higher-affinity thresholds for both B cell antigen receptor (BCR) signaling and antigen gathering as compared with naïve B cells and that these functions are mediated by distinct cellular structures and pathways that ultimately lead to antigen affinity– and Tfh cell–dependent differentiation to plasma cells. GC B cells bound antigen through highly dynamic, actin- and ezrin-rich pod-like structures that concentrated BCRs. The behavior of these structures was dictated by the intrinsic antigen affinity thresholds of GC B cells. Low-affinity antigens triggered continuous engagement and disengagement of membrane-associated antigens, whereas high-affinity antigens induced stable synapse formation. The pod-like structures also mediated affinity-dependent antigen internalization by unconventional pathways distinct from those of naïve B cells. Thus, intrinsic properties of human GC B cells set thresholds for affinity selection.