TY - JOUR
T1 - The Eph-related tyrosine kinase ligand Ephrin-B1 marks germinal center and memory precursor B cells
AU - Laidlaw, Brian J.
AU - Schmidt, Timothy H.
AU - Green, Jesse A.
AU - Allen, Christopher D.C.
AU - Okada, Takaharu
AU - Cyster, Jason G.
N1 - Publisher Copyright:
© 2017 Laidlaw et al.
PY - 2017/3/6
Y1 - 2017/3/6
N2 - Identification of germinal center (GC) B cells is typically reliant on the use of surface activation markers that exhibit a wide range of expression. Here, we identify Ephrin-B1, a ligand for Eph-related receptor tyrosine kinases, as a specific marker of mature GC B cells. The number of Ephrin-B1+ GC B cells increases during the course of an immune response with Ephrin-B1+ GC B cells displaying elevated levels of Bcl6, S1pr2, and Aicda relative to their Ephrin-B1- counterparts. We further identified a small proportion of recently dividing, somatically mutated Ephrin-B1+ GC B cells that have begun to down-regulate Bcl6 and S1pr2 and express markers associated with memory B cells, such as CD38 and EBI2. Transcriptional analysis indicates that these cells are developmentally related to memory B cells, and likely represent a population of GC memory precursor (PreMem) B cells. GC PreMem cells display enhanced survival relative to bulk GC B cells, localize near the edge of the GC, and are predominantly found within the light zone. These findings offer insight into the significant heterogeneity that exists within the GC B cell population and provide tools to further dissect signals regulating the differentiation of GC B cells.
AB - Identification of germinal center (GC) B cells is typically reliant on the use of surface activation markers that exhibit a wide range of expression. Here, we identify Ephrin-B1, a ligand for Eph-related receptor tyrosine kinases, as a specific marker of mature GC B cells. The number of Ephrin-B1+ GC B cells increases during the course of an immune response with Ephrin-B1+ GC B cells displaying elevated levels of Bcl6, S1pr2, and Aicda relative to their Ephrin-B1- counterparts. We further identified a small proportion of recently dividing, somatically mutated Ephrin-B1+ GC B cells that have begun to down-regulate Bcl6 and S1pr2 and express markers associated with memory B cells, such as CD38 and EBI2. Transcriptional analysis indicates that these cells are developmentally related to memory B cells, and likely represent a population of GC memory precursor (PreMem) B cells. GC PreMem cells display enhanced survival relative to bulk GC B cells, localize near the edge of the GC, and are predominantly found within the light zone. These findings offer insight into the significant heterogeneity that exists within the GC B cell population and provide tools to further dissect signals regulating the differentiation of GC B cells.
UR - http://www.scopus.com/inward/record.url?scp=85016232208&partnerID=8YFLogxK
U2 - 10.1084/jem.20161461
DO - 10.1084/jem.20161461
M3 - Article
C2 - 28143955
AN - SCOPUS:85016232208
SN - 0022-1007
VL - 214
SP - 639
EP - 649
JO - The Journal of experimental medicine
JF - The Journal of experimental medicine
IS - 3
ER -