title: Development of functional B cells in a line of SCID mice with transgenes coding for anti-double-stranded DNA antibody.
abstract: Deletion or inactivation of anti-self (DNA) B cells has been reported in non-autoimmune mice bearing Ig transgenes that code for Abs with specificity for dsDNA or ssDNA. However, we report a case in which anti-dsDNA B cells appear to escape both deletion and inactivation. We show that B cells (B220+IgM+) can develop in non-autoimmune SCID mice bearing two site-directed transgenes, 3H9(56R) and Vkappa8, that together code for an anti-dsDNA Ab. The B cells appear inactive, because the mice (56RVkappa8 SCID mice) generally lack serum Ig. However, 56RVkappa8 SCID mice are able to produce IgG Ab with specificity for dsDNA when they become "leaky" for T cells or are reconstituted with exogenous T cells from B cell-deficient JH-/- donors. Thus, anti-dsDNA B cells that escape deletion in 56RVkappa8 SCID mice appear fully functional and can differentiate, class switch, and give rise to IgG-producing cells in the presence of T cells and self-Ag.
authors.affiliation: Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Gayle C
authors.initials: GC
authors.lastname: Bosma
authors.forename: Jennifer
authors.initials: J
authors.lastname: Oshinsky
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kiefer
authors.forename: Pamela B
authors.initials: PB
authors.lastname: Nakajima
authors.forename: Deepshika
authors.initials: D
authors.lastname: Charan
authors.forename: Cecil
authors.initials: C
authors.lastname: Congelton
authors.forename: Marko
authors.initials: M
authors.lastname: Radic
authors.forename: Melvin J
authors.initials: MJ
authors.lastname: Bosma
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000235:genetics*; D000918:Antibody Specificity; D001324:Autoantigens; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D004247:DNA / Q000276:immunology; D005803:Genes, Immunoglobulin; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D001324:Autoantigens; D007074:Immunoglobulin G; D004247:DNA