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.