title: Targeting of Ly9 (CD229) Disrupts Marginal Zone and B1 B Cell Homeostasis and Antibody Responses.
abstract: Marginal zone (MZ) and B1 B cells have the capacity to respond to foreign Ags more rapidly than conventional B cells, providing early immune responses to blood-borne pathogens. Ly9 (CD229, SLAMF3), a member of the signaling lymphocytic activation molecule family receptors, has been implicated in the development and function of innate T lymphocytes. In this article, we provide evidence that in Ly9-deficient mice splenic transitional 1, MZ, and B1a B cells are markedly expanded, whereas development of B lymphocytes in bone marrow is unaltered. Consistent with an increased number of these B cell subsets, we detected elevated levels of IgG3 natural Abs and a striking increase of T-independent type II Abs after immunization with 2,4,6-trinitrophenyl-Ficoll in the serum of Ly9-deficient mice. The notion that Ly9 could be a negative regulator of innate-like B cell responses was supported by the observation that administering an mAb directed against Ly9 to wild-type mice selectively eliminated splenic MZ B cells and significantly reduced the numbers of B1 and transitional 1 B cells. In addition, Ly9 mAb dramatically diminished in vivo humoral responses and caused a selective downregulation of the CD19/CD21/CD81 complex on B cells and concomitantly an impaired B cell survival and activation in an Fc-independent manner. We conclude that altered signaling caused by the absence of Ly9 or induced by anti-Ly9 may negatively regulate development and function of innate-like B cells by modulating B cell activation thresholds. The results suggest that Ly9 could serve as a novel target for the treatment of B cell-related diseases.
authors.affiliation: Immunology Unit, Department of Cell Biology, Immunology and Neurosciences, Medical School, University of Barcelona, Barcelona 08036, Spain; and.
authors.forename: Marta
authors.initials: M
authors.lastname: Cuenca
authors.affiliation: Immunology Unit, Department of Cell Biology, Immunology and Neurosciences, Medical School, University of Barcelona, Barcelona 08036, Spain; and.
authors.forename: Xavier
authors.initials: X
authors.lastname: Romero
authors.affiliation: Immunology Unit, Department of Cell Biology, Immunology and Neurosciences, Medical School, University of Barcelona, Barcelona 08036, Spain; and.
authors.forename: Jordi
authors.initials: J
authors.lastname: Sintes
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.
authors.forename: Cox
authors.initials: C
authors.lastname: Terhorst
authors.affiliation: Immunology Unit, Department of Cell Biology, Immunology and Neurosciences, Medical School, University of Barcelona, Barcelona 08036, Spain; and pengel@ub.edu.
authors.forename: Pablo
authors.identifier: http://orcid.org/0000-0001-8410-252X
authors.initials: P
authors.lastname: Engel
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D000071176:Signaling Lymphocytic Activation Molecule Family; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D015703:Antigens, CD; C498972:Ly9 protein, mouse; D000071176:Signaling Lymphocytic Activation Molecule Family