title: Dual-reactive B cells are autoreactive and highly enriched in the plasmablast and memory B cell subsets of autoimmune mice.
abstract: Rare dual-reactive B cells expressing two types of Ig light or heavy chains have been shown to participate in immune responses and differentiate into IgG(+) cells in healthy mice. These cells are generated more often in autoreactive mice, leading us to hypothesize they might be relevant in autoimmunity. Using mice bearing Igk allotypic markers and a wild-type Ig repertoire, we demonstrate that the generation of dual-κ B cells increases with age and disease progression in autoimmune-prone MRL and MRL/lpr mice. These dual-reactive cells express markers of activation and are more frequently autoreactive than single-reactive B cells. Moreover, dual-κ B cells represent up to half of plasmablasts and memory B cells in autoimmune mice, whereas they remain infrequent in healthy mice. Differentiation of dual-κ B cells into plasmablasts is driven by MRL genes, whereas the maintenance of IgG(+) cells is partly dependent on Fas inactivation. Furthermore, dual-κ B cells that differentiate into plasmablasts retain the capacity to secrete autoantibodies. Overall, our study indicates that dual-reactive B cells significantly contribute to the plasmablast and memory B cell populations of autoimmune-prone mice suggesting a role in autoimmunity.
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado, Denver School of Medicine, Denver, CO 80206, USA.
authors.forename: Emilie M
authors.initials: EM
authors.lastname: Fournier
authors.forename: Maria-Gabriela
authors.initials: MG
authors.lastname: Velez
authors.forename: Katelyn
authors.initials: K
authors.lastname: Leahy
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Swanson
authors.forename: Anatoly V
authors.initials: AV
authors.lastname: Rubtsov
authors.forename: Raul M
authors.initials: RM
authors.lastname: Torres
authors.forename: Roberta
authors.initials: R
authors.lastname: Pelanda
mesh_terms: D000367:Age Factors; D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D060966:Clonal Selection, Antigen-Mediated / Q000235:genetics / Q000276:immunology; D005260:Female; D006825:Hybridomas / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies; C014609:IgK; D007074:Immunoglobulin G; D007136:Immunoglobulins; D051199:Toll-Like Receptor 7; D019014:fas Receptor