title: Autoreactive IgG memory antibodies in patients with systemic lupus erythematosus arise from nonreactive and polyreactive precursors.
abstract: Persistent autoantibody production in patients with systemic lupus erythematosus (SLE) suggests the existence of autoreactive humoral memory, but the frequency of self-reactive memory B cells in SLE has not been determined. Here, we report on the reactivity of 200 monoclonal antibodies from single IgG+ memory B cells of four SLE patients. The overall frequency of polyreactive and HEp-2 self-reactive antibodies in this compartment was similar to controls. We found 15% of IgG memory B cell antibodies highly reactive and specific for SLE-associated extractable nuclear antigens (ENA) Ro52 and La in one patient with serum autoantibody titers of the same specificity but not in the other three patients or healthy individuals. The germ-line forms of the ENA antibodies were non-self-reactive or polyreactive with low binding to Ro52, supporting the idea that somatic mutations contributed to autoantibody specificity and reactivity. Heterogeneity in the frequency of memory B cells expressing SLE-associated autoantibodies suggests that this variable may be important in the outcome of therapies that ablate this compartment.
authors.affiliation: Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
authors.forename: Brun
authors.initials: B
authors.lastname: Mietzner
authors.forename: Makoto
authors.initials: M
authors.lastname: Tsuiji
authors.forename: Johannes
authors.initials: J
authors.lastname: Scheid
authors.forename: Klara
authors.initials: K
authors.lastname: Velinzon
authors.forename: Thomas
authors.initials: T
authors.lastname: Tiller
authors.forename: Klaus
authors.initials: K
authors.lastname: Abraham
authors.forename: Jose B
authors.initials: JB
authors.lastname: Gonzalez
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual
authors.forename: Dorothee
authors.initials: D
authors.lastname: Stichweh
authors.forename: Hedda
authors.initials: H
authors.lastname: Wardemann
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000918:Antibody Specificity; D034961:Antigens, Nuclear; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G; D007156:Immunologic Memory; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D012261:Ribonucleoproteins / Q000276:immunology; D000097585:SS-B Antigen; D000099207:SS-A Antigen
chemical_list: D034961:Antigens, Nuclear; D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen