title: Naturally occurring human phosphorylcholine antibodies are predominantly products of affinity-matured B cells in the adult.
abstract: Phosphorylcholine (PC) is a classic T-independent Ag that is exposed on apoptotic cells, oxidized phospholipids, and bacterial polysaccharides. Experimental as well as epidemiological studies have over the past decade implicated Abs against PC (anti-PC) as anti-inflammatory and a strong protective factor in cardiovascular disease. Although clinically important, little is known about the development of anti-PC in humans. This study was conceived to dissect the human anti-PC repertoire and generate human mAbs. We designed a PC-specific probe to identify, isolate, and characterize PC-reactive B cells from 10 healthy individuals. The donors had all mounted somatically mutated Abs toward PC using a broad variety of Ig genes. PC-reactive B cells were primarily found in the IgM(+) memory subset, although significant numbers also were detected among naive, IgG(+), and CD27(+)CD43(+) B cells. Abs from these subsets were clonally related, suggesting a common origin. mAbs derived from the same donors exhibited equivalent or higher affinity for PC than the well-characterized murine T-15 clone. These results provide novel insights into the cellular and molecular ontogeny of atheroprotective PC Abs, thereby offering new opportunities for Ab-based therapeutic interventions.
authors.affiliation: Unit of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors.forename: Roland
authors.initials: R
authors.lastname: Fiskesund
authors.forename: Johanna
authors.initials: J
authors.lastname: Steen
authors.forename: Khaled
authors.initials: K
authors.lastname: Amara
authors.forename: Fiona
authors.initials: F
authors.lastname: Murray
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szwajda
authors.forename: Anquan
authors.initials: A
authors.lastname: Liu
authors.forename: Iyadh
authors.initials: I
authors.lastname: Douagi
authors.forename: Vivianne
authors.initials: V
authors.lastname: Malmström
authors.forename: Johan
authors.initials: J
authors.lastname: Frostegård
mesh_terms: D000328:Adult; D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology*; D007156:Immunologic Memory / Q000502:physiology*; D008297:Male; D051379:Mice; D010767:Phosphorylcholine / Q000276:immunology*
chemical_list: D017152:Antibodies, Antiphospholipid; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010767:Phosphorylcholine