Internalization of B cell receptors in human EU12 μHC⁺ immature B cells specifically alters downstream signaling events

Biomed Res Int. 2013:2013:807240. doi: 10.1155/2013/807240. Epub 2013 Oct 9.

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 EU12 μHC⁺ immature B cells resulted in complete internalization of cell surface BCRs. After loss of cell surface BCRs, restimulation of EU12 μHC⁺ 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 EU12 μHC⁺ cells after BCR internalization. Taken together, these results show that complete internalization of cell surface BCRs in EU12 μHC⁺ cells specifically alters the downstream signaling events, which may favor receptor editing versus cell activation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, CD19 / immunology
  • Antigens, CD19 / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / immunology
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Phosphorylation / immunology
  • Protein-Tyrosine Kinases / immunology
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Antigen, B-Cell / metabolism*
  • Signal Transduction / immunology*
  • Surface Properties
  • Syk Kinase

Substances

  • Antigens, CD19
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Antigen, B-Cell
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase