B Cell Receptor Crosslinking Augments Germinal Center B Cell Selection when T Cell Help Is Limiting

Abstract

Summary: Antigen-dependent engagement of germinal center (GC) B cell receptors (BCRs) promotes antigen internalization and presentation for follicular helper T cells. However, whether BCR signaling is critical or synergistic with T cell help for GC B cell selection or differentiation is unclear. Here, by adapting an experimental approach that enables independent delivery of BCR-crosslinking antigen or T cell help to GC B cells in vivo, we showed that T cell help was sufficient to induce GC B cell expansion and plasmablast formation. However, although BCR crosslinking could not by itself promote GC B cell selection or differentiation, it could synergize with T cell help to enhance the GC and plasmablast responses when T cell help was limiting. These findings indicate that GC B cells can integrate variable inputs from T cell help and BCR signaling in vivo for an optimal process of selection and differentiation, critical for potent long-term humoral immunity. : Turner et al. show that recurrent antigen-dependent BCR crosslinking is not required for GC centrocytes selection and differentiation into plasmablasts in vivo. However, when T cell help is subsaturating, BCR signaling can synergize with follicular T cell help to potentiate GC B cell selection and their differentiation into plasmablasts. Keywords: germinal centers, follicular helper T cells, B cell receptor, T cell help, B cell selection and differentiation, plasma cells