Internalization of B Cell Receptors in Human EU12μHC+Immature B Cells Specifically Alters Downstream Signaling Events

Abstract

It has been recognized for a long time that engagement of B cell antigen receptors (BCRs) on immature B cells or mature B cells leads to completely opposite cell fate decisions. The underlying mechanism remains unclear. Here, we show that crosslinking of BCRs on human EU12μHC+immature B cells resulted in complete internalization of cell surface BCRs. After loss of cell surface BCRs, restimulation of EU12μHC+cells showed impaired Ca2+flux, delayed SYK phosphorylation, and decreased CD19 and FOXO1 phosphorylation, which differ from those in mature Daudi or Ramos B cells with partial internalization of BCRs. In contrast, sustained phosphorylation and reactivation of ERK upon restimulation were observed in the EU12μHC+cells after BCR internalization. Taken together, these results show that complete internalization of cell surface BCRs in EU12μHC+cells specifically alters the downstream signaling events, which may favor receptor editing versus cell activation.