TGF? signaling in germinal center B cells promotes the transition from light zone to dark zone.

ABSTRACT: B cells in germinal centers (GCs) cycle between light zone (LZ) and dark zone (DZ). The cues in the GC microenvironment that regulate the transition from LZ to DZ have not been well characterized. In Peyer's patches (PPs), transforming growth factor-? (TGF?) promotes IgA induction in activated B cells that can then differentiate into GC B cells. We show here that TGF? signaling occurs in B cells in GCs and is distinct from signaling that occurs in activated B cells in PPs. Whereas in activated B cells TGF? signaling is required for IgA induction, in the GC it was instead required for the transition from LZ to DZ. In the absence of TGF? signaling, there was an accumulation of LZ GC B cells and reduced antibody affinity maturation likely due to reduced activation of Foxo1. This work identifies TGF? as a microenvironmental cue that is critical for GC homeostasis and function.

SUBMITTER: Albright AR 

PROVIDER: S-EPMC6829600 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature