title: Primary development and participation in a foreign antigen-driven immune response of a chromatin-reactive B cell clonotype are not influenced by TLR9 or other MyD88-dependent TLRs.
abstract: Recent findings support a central role for TLRs in both foreign Ag-driven immune responses and systemic autoimmune diseases mediated by B lymphocytes. In vitro studies have shown that the Ag receptors (BCRs) on B cells specific for nuclear autoantigens can facilitate the delivery of these autoantigens to the endocytic compartment, resulting in activation of the nucleic acid-specific TLRs present in this subcellular locale. If this pathway is operative in vivo it might promote the development, survival, or activation of such autoreactive B cells. To test this idea, we evaluated the influence of a deficiency in the CpG DNA-specific TLR, TLR9, or all MyD88-dependent TLRs on the primary development and foreign Ag-driven immune response of B cells in a line of V(H) knockin mice that contains a high frequency of "dual reactive" B cells specific for DNA-based autoantigens such as chromatin, as well as the hapten arsonate. We found that although development and activation of these B cells in vitro are clearly influenced by DNA-based autoantigens, TLR9 or MyD88 deficiencies had no apparent effect on the primary development and participation in the anti-arsonate response of these B cells in vivo. We discuss these results in the context of previous models for the role of TLR9 and other TLRs in the regulation of antinuclear Ag B cell development and activity.
authors.affiliation: Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Coffey
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Liu
authors.forename: Tim
authors.initials: T
authors.lastname: Manser
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000276:immunology*; D001152:Arsenicals / Q000276:immunology / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002843:Chromatin / Q000276:immunology*; D018899:CpG Islands / Q000276:immunology; D006241:Haptens / Q000276:immunology / Q000494:pharmacology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology*
chemical_list: D034961:Antigens, Nuclear; D001152:Arsenicals; D002843:Chromatin; D006241:Haptens; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011947:Receptors, Antigen, B-Cell; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; C054806:arsonic acid