Membrane immunoglobulin expressed by retroviral vector gene transfer mimics partial function of the B-cell receptor in vivo

Sci China Life Sci. 2016 Jan;59(1):49-58. doi: 10.1007/s11427-015-4931-3. Epub 2015 Oct 19.

Abstract

Activation of B-cells is initiated by the ligation of B-cell receptors by its cognate antigen, inducing a series of signal cascades. Understanding the molecular mechanisms of these important events is a crucial goal for immunologists. Chimeric B cell receptors provide a powerful tool for analysis of B-cell signal function. However, this method can only be used in tool cells, but cannot be used for in vivo study. Here, we constructed a retroviral vector to encode both heavy chains and light chains of a membrane immunoglobulin, and expressed them in primary B-cells using retroviral gene transfer. Our results demonstrate that the membrane immunoglobulin expressed by retroviral vectors transfer can initiate B-cell receptor-mediated signaling, resulting in the phosphorylation of Syk and Erk1/2 proteins. The results showed that B-cells expressing membrane immunoglobulin can make proliferative responses to cognate antigen both in vitro and in vivo. Therefore, we provide a methodology for rapidly analyzing the downstream signals of B-cell receptors both in vitro and in vivo, which could expedite the identification of proteins involved in B-cell function.

Keywords: BCR; membrane immunoglobulin; retroviral vector.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Proliferation
  • Gene Transfer Techniques
  • Genetic Vectors
  • Green Fluorescent Proteins / genetics
  • Humans
  • Immunoglobulins / genetics*
  • Immunoglobulins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • NIH 3T3 Cells
  • Phosphorylation
  • Receptors, Antigen, B-Cell / genetics*
  • Receptors, Antigen, B-Cell / metabolism*
  • Retroviridae / genetics
  • Signal Transduction

Substances

  • Immunoglobulins
  • Membrane Proteins
  • Receptors, Antigen, B-Cell
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins