Retroviral Overexpression of CXCR4 on Murine B-1a Cells and Adoptive Transfer for Targeted B-1a Cell Migration to the Bone Marrow and IgM Production

J Vis Exp. 2020 May 31:(159):10.3791/61003. doi: 10.3791/61003.

Abstract

As cell function is influenced by niche-specific factors in the cellular microenvironment, methods to dissect cell localization and migration can provide further insight on cell function. B-1a cells are a unique B cell subset in mice that produce protective natural IgM antibodies against oxidation-specific epitopes that arise during health and disease. B-1a cell IgM production differs depending on B-1a cell location, and therefore it becomes useful from a therapeutic standpoint to target B-1a localization to niches supportive of high antibody production. Here we describe a method to target B-1a cell migration to the bone marrow by retroviral-mediated overexpression of the C-X-C motif chemokine receptor 4 (CXCR4). Gene induction in primary murine B cells can be challenging and typically yields low transfection efficiencies of 10-20% depending on technique. Here we demonstrate that retroviral transduction of primary murine B-1a cells results in 30-40% transduction efficiency. This method utilizes adoptive cell transfer of transduced B-1a cells into B cell-deficient recipient mice so that donor B-1a cell migration and localization can be visualized. This protocol can be modified for other retroviral constructs and can be used in diverse functional assays post-adoptive transfer, including analysis of donor cell or host cell phenotype and function, or analysis of soluble factors secreted post B-1a cell transfer. The use of distinct donor and recipient mice differentiated by CD45.1 and CD45.2 allotype and the presence of a GFP reporter within the retroviral plasmid could also enable detection of donor cells in other, immune-sufficient mouse models containing endogenous B cell populations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Adoptive Transfer*
  • Animals
  • Antibody Formation
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / immunology
  • Bone Marrow Cells / immunology*
  • Cell Differentiation
  • Cell Movement*
  • Immunoglobulin M / immunology
  • Leukocyte Common Antigens
  • Mice
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*
  • Retroviridae / metabolism*
  • Signal Transduction

Substances

  • CXCR4 protein, mouse
  • Immunoglobulin M
  • Receptors, CXCR4
  • Leukocyte Common Antigens
  • PTPRC protein, human