title: The Eph-related tyrosine kinase ligand Ephrin-B1 marks germinal center and memory precursor B cells.
abstract: 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, andAicdarelative 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 andS1pr2and 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.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143.|Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Laidlaw
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143.|Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Timothy H
authors.identifier: 0000-0003-3991-0012
authors.initials: TH
authors.lastname: Schmidt
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143.|Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Jesse A
authors.initials: JA
authors.lastname: Green
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143.|Department of Anatomy, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143.|Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Christopher D C
authors.identifier: 0000-0002-1879-9047
authors.initials: CD
authors.lastname: Allen
authors.affiliation: Laboratory for Tissue Dynamics, Institute of Physical and Chemical Research Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Okada
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143 jason.cyster@ucsf.edu.|Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Jason G
authors.identifier: 0000-0002-4735-9745
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers; D036387:Ephrin-B1 / Q000032:analysis / Q000502:physiology*; D018858:Germinal Center / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D049349:Receptors, Lysosphingolipid / Q000032:analysis; D000081025:Sphingosine-1-Phosphate Receptors; D053668:Syndecan-1 / Q000032:analysis
chemical_list: D015415:Biomarkers; D036387:Ephrin-B1; D049349:Receptors, Lysosphingolipid; C508242:Sdc1 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors; D053668:Syndecan-1; C533955:sphingosine-1-phosphate receptor-2, mouse