Positive Selection in the Light Zone of Germinal Centers

Abstract

Germinal centers (GCs) are essential sites for the production of high-affinity antibody secreting plasma cells (PCs) and memory-B cells (MBCs), which form the framework of vaccination. Affinity maturation and permissive selection in GCs are key for the production of PCs and MBCs, respectively. For these purposes, GCs positively select "fit" cells in the light zone of the GC and instructs them for one of three known B cell fates: PCs, MBCs and persistent GC-B cells as dark zone entrants. In this review, we provide an overview of the positive selection process and discuss its mechanisms and how B cell fates are instructed.

Keywords: affinity maturation; cMyc; clonal diversity; permissive selection; positive selection.

Figure 1

Proposed model of permissive positive selection in GCs. GC-B cells compete for antigen when only limited amount of antigen (Ag) is available. Fit cells retrieve Ag deposited on follicular dendritic cells (FDCs) relatively independently of BCR affinity and receive survival signals from FDCs through contact-based interaction and/or trophic factors. Both high and low-affinity cells process Ag and present differing levels of Ag in the form of peptide-MHCII complex (pMHC) in proportion to its affinity. Low-affinity cells may augment the level of signaling above a threshold with potentially undefined mechanisms, such as favorably augmented signals and/or less negative feedback. GC-B cells received sufficient signals for positive selection proliferate mainly based on their BCR affinity. Their fates are also instructed, generally depending on their BCR affinity. cMyc⁺ GC-B cells divide in the LZ and cMyc expression in GC-B cells is reduced accordingly. The width of the arrows in GC-B cells and TFH depicts the signal strength.