title: CD80 and PD-L2 define functionally distinct memory B cell subsets that are independent of antibody isotype.
abstract: Memory B cells (MBCs) are long-lived sources of rapid, isotype-switched secondary antibody-forming cell (AFC) responses. Whether MBCs homogeneously retain the ability to self-renew and terminally differentiate or if these functions are compartmentalized into MBC subsets has remained unclear. It has been suggested that antibody isotype controls MBC differentiation upon restimulation. Here we demonstrate that subcategorizing MBCs on the basis of their expression of CD80 and PD-L2, independently of isotype, identified MBC subsets with distinct functions upon rechallenge. CD80(+)PD-L2(+) MBCs differentiated rapidly into AFCs but did not generate germinal centers (GCs); conversely, CD80(-)PD-L2(-) MBCs generated few early AFCs but robustly seeded GCs. The gene-expression patterns of the subsets supported both the identity and function of these distinct MBC types. Hence, the differentiation and regeneration of MBCs are compartmentalized.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Griselda V
authors.initials: GV
authors.lastname: Zuccarino-Catania
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Saheli
authors.initials: S
authors.lastname: Sadanand
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Florian J
authors.initials: FJ
authors.lastname: Weisel
authors.affiliation: Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Tomayko
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Hailong
authors.initials: H
authors.lastname: Meng
authors.affiliation: 1] Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut, USA.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Kleinstein
authors.affiliation: 1] Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. [3].
authors.forename: Kim L
authors.initials: KL
authors.lastname: Good-Jacobson
authors.affiliation: 1] Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. [3].
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shlomchik
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000921:Antibody-Producing Cells / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D018122:B7-1 Antigen / Q000502:physiology*; D018858:Germinal Center / Q000276:immunology; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000502:physiology*; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D018122:B7-1 Antigen; D007132:Immunoglobulin Isotypes; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein