Capturing change in clonal composition amongst single mouse germinal centers

Elife. 2018 Aug 1:7:e33051. doi: 10.7554/eLife.33051.


Understanding cellular processes occurring in vivo on time scales of days to weeks requires repeatedly interrogating the same tissue without perturbing homeostasis. We describe a novel setup for longitudinal intravital imaging of murine peripheral lymph nodes (LNs). The formation and evolution of single germinal centers (GCs) was visualized over days to weeks. Naïve B cells encounter antigen and form primary foci, which subsequently seed GCs. These experience widely varying rates of homogenizing selection, even within closely confined spatial proximity. The fluidity of GCs is greater than previously observed with large shifts in clonality over short time scales; and loss of GCs is a rare, observable event. The observation of contemporaneous, congruent shifts in clonal composition between GCs within the same animal suggests inter-GC trafficking of memory B cells. This tool refines approaches to resolving immune dynamics in peripheral LNs with high temporospatial resolution and minimal perturbation of homeostasis.

Keywords: B cell clonal development; germinal centers; immunology; inflammation; intravital imaging; mouse.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / physiology
  • Cell Movement
  • Cells, Cultured
  • Clonal Evolution*
  • Clonal Selection, Antigen-Mediated / immunology*
  • Germinal Center / cytology*
  • Germinal Center / immunology
  • Germinal Center / physiology
  • Lymph Nodes / cytology*
  • Lymph Nodes / immunology
  • Lymph Nodes / physiology
  • Mice
  • Mice, Inbred C57BL
  • Time-Lapse Imaging