Germinal Center Formation with Retrovirally Transduced B Cells for Determining the Role of Specific Molecules In Vivo

Methods Mol Biol. 2017:1623:147-158. doi: 10.1007/978-1-4939-7095-7_13.

Abstract

Retrovirus-mediated gene transfer has become a powerful tool to investigate roles of specific molecules in B cells, due to its efficiency and expeditiousness. This technology is applicable to activated B cells in order to determine effects of a gene of interest during germinal center (GC) reactions in combination with adoptive transfer. To achieve this, B cells derived from SWHEL mice expressing hen egg lysozyme (HEL)-specific B cell receptors (BCR) are stimulated with HEL antigen in vivo and then with anti-CD40 antibody ex vivo. These cells are then transduced with a retrovirus allowing bicistronic co-expression of a gene of interest and GFP, enabling differentiation of transgene positive cells. The retrovirally transduced cells are then adoptively transferred into immunized CD45.1+ congenic recipient mice, to enable differentiation between donor and host cells. This chapter describes methods for (1) activation of HEL-specific mature B cells, (2) retroviral transduction of the activated B cells, (3) adoptive transfer of the cells into recipients, and (4) analysis of the resultant mice by flow cytometry.

Keywords: Adoptive transfer; Antigen-specific B cells; GC-B cells; HEL; PEG-it; Retroviral transduction; SWHEL.

MeSH terms

  • Adaptive Immunity
  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / metabolism*
  • Biomarkers
  • Cell Line
  • Cells, Cultured
  • Epitopes, B-Lymphocyte / immunology
  • Flow Cytometry
  • Genetic Vectors / genetics
  • Germinal Center / cytology*
  • Germinal Center / immunology
  • Germinal Center / metabolism*
  • Humans
  • Mice
  • Muramidase / immunology
  • Retroviridae / genetics
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • Transduction, Genetic*
  • Transgenes

Substances

  • Biomarkers
  • Epitopes, B-Lymphocyte
  • hen egg lysozyme
  • Muramidase