title: Types of tolerance seen in autoreactive phosphocholine-specific B cells are dependent on the idiotype of the receptors expressed.
abstract: Phosphocholine (PC) is the immunodominant epitope found on the surface of a number of microorganisms, including Streptococcus pneumoniae (SPn), and is thought to play a vital role in the pathogenesis of SPn. B cells expressing M167Hκ24L immunoglobulin receptors specific for PC have been shown to be autoreactive in that they undergo clonal deletion in both X-linked immune-deficient and Rag(-/-) mice. We have now shown that B cells expressing M603Hκ8L PC-specific receptors also delete in Rag(-/-) mice, whereas those expressing T15Hκ22L transgenes do not delete. However, T15Hκ22L B cells are lost in normal heterozygous transgenic mice because they cannot compete with normal B cells. These data indicate that M167Hκ24L and M603Hκ8L PC-specific B cells are recognizing an autoantigen expressed on membranes which causes them to downregulate their receptors and clonally delete, while T15Hκ22L B cells are tolerized by a soluble form of PC-antigen which results in their being trapped in the spleen. Thus, the types of tolerance seen in autoreactive PC-specific B cells are dependent on the idiotype of the receptors expressed.
authors.affiliation: Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI, USA. qmi1@hfhs.org
authors.forename: Qing-Sheng
authors.initials: QS
authors.lastname: Mi
authors.forename: James J
authors.initials: JJ
authors.lastname: Kenny
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D017637:Clonal Deletion; D004268:DNA-Binding Proteins / Q000235:genetics; D005434:Flow Cytometry; D007108:Immune Tolerance; D007130:Immunoglobulin Idiotypes / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010767:Phosphorylcholine / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D013290:Streptococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001324:Autoantigens; D004268:DNA-Binding Proteins; D007130:Immunoglobulin Idiotypes; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; D010767:Phosphorylcholine