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J Immunol. 2014 May 15;192(10):4551-9. doi: 10.4049/jimmunol.1303035. Epub 2014 Apr 11.

Naturally occurring human phosphorylcholine antibodies are predominantly products of affinity-matured B cells in the adult.

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  • 1Unit of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden;

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.

PMID:
24729615
[PubMed - indexed for MEDLINE]
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