Capturing change in clonal composition amongst single mouse germinal centers

TY - JOUR

T1 - Capturing change in clonal composition amongst single mouse germinal centers

AU - Firl, Daniel J

AU - Degn, Soren E

AU - Padera, Timothy

AU - Carroll, Michael C

N1 - © 2018, Firl et al.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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.

AB - 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.

KW - ACTIVATION

KW - B-CELL TOLERANCE

KW - DYNAMICS

KW - HOMEOSTASIS

KW - INDUCED CYTIDINE DEAMINASE

KW - LONG-TERM

KW - MEMORY

KW - MICROSCOPY

KW - REVEALS

KW - WINDOW

UR - http://www.scopus.com/inward/record.url?scp=85053909223&partnerID=8YFLogxK

U2 - 10.7554/eLife.33051

DO - 10.7554/eLife.33051

M3 - Journal article

C2 - 30066671

SN - 2050-084X

VL - 7

JO - eLife

JF - eLife

M1 - e33051

ER -