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

Abstract

Antigen-dependent engagement of germinal center (GC) B cell receptors (BCRs) promotes antigen internalization and presentation for follicular helper Tcells. However, whether BCR signaling is critical or synergistic with Tcell 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 Tcell help to GC B cells invivo, we showed that Tcell 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 Tcell help to enhance the GC and plasmablast responses when Tcell help was limiting. These findings indicate that GC B cells can integrate variable inputs from Tcell help and BCR signaling invivo for an optimal process of selection and differentiation, critical for potent long-term humoral immunity.