title: Dermatan sulfate interacts with dead cells and regulates CD5(+) B-cell fate: implications for a key role in autoimmunity.
abstract: CD5(+) (B-1a) B cells play pivotal roles in autoimmunity through expression of autoreactive B-cell receptors and production of autoantibodies. The mechanism underlying their positive selection and expansion is currently unknown. This study demonstrates that dermatan sulfate (DS) expands the B-1a cell population and augments the specific antibody response to an antigen when it is in complex with DS. DS displays preferential affinity for apoptotic and dead cells, and DS-stimulated cell cultures produce antibodies to various known autoantigens. The companion article further illustrates that autoantigens can be identified by affinity to DS, suggesting that molecules with affinity to DS have a high propensity to become autoantigens. We thus propose that the association of antigens from dead cells with DS is a possible origin of autoantigens and that autoreactive B-1a cells are positively selected and expanded by DS∙autoantigen complexes. This mechanism may also explain the clonal expansion of B-1a cells in certain B-cell malignancies.
authors.affiliation: Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Julia Y
authors.initials: JY
authors.lastname: Wang
authors.forename: Jongmin
authors.initials: J
authors.lastname: Lee
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Jung-hyun
authors.initials: JH
authors.lastname: Rho
authors.forename: Michael H A
authors.initials: MH
authors.lastname: Roehrl
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D018956:CD5 Antigens / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D003871:Dermatan Sulfate / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron
chemical_list: D018941:Antigens, CD19; D001324:Autoantigens; D018956:CD5 Antigens; D003871:Dermatan Sulfate