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JCI Insight. 2019 May 16;4(10). pii: 122551. doi: 10.1172/jci.insight.122551. eCollection 2019 May 16.

Self-tolerance curtails the B cell repertoire to microbial epitopes.

Author information

1
Department of Immunology, Duke University School of Medicine, Durham, North Carolina, USA.
2
Tzu Chi Medical Center, Hualien, Taiwan.
3
Deparment of Microbiology, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
4
Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
5
Laboratory of Molecular Medicine, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
6
Howard Hughes Medical Institute, Boston, Massachusetts, USA.
7
Duke Human Vaccine Institute and.
8
Department of Medicine, Duke University, Durham, North Carolina, USA.

Abstract

Immunological tolerance removes or inactivates self-reactive B cells, including those that also recognize cross-reactive foreign antigens. Whereas a few microbial pathogens exploit these "holes" in the B cell repertoire by mimicking host antigens to evade immune surveillance, the extent to which tolerance reduces the B cell repertoire to foreign antigens is unknown. Here, we use single-cell cultures to determine the repertoires of human B cell antigen receptors (BCRs) before (transitional B cells) and after (mature B cells) the second B cell tolerance checkpoint in both healthy donors and in patients with systemic lupus erythematosus (SLE) . In healthy donors, the majority (~70%) of transitional B cells that recognize foreign antigens also bind human self-antigens (foreign+self), and peripheral tolerance halves the frequency of foreign+self-reactive mature B cells. In contrast, in SLE patients who are defective in the second tolerance checkpoint, frequencies of foreign+self-reactive B cells remain unchanged during maturation of transitional to mature B cells. Patterns of foreign+self-reactivity among mature B cells from healthy donors differ from those of SLE patients. We propose that immune tolerance significantly reduces the scope of the BCR repertoire to microbial pathogens and that cross-reactivity between foreign and self epitopes may be more common than previously appreciated.

KEYWORDS:

B cells; Immunology; Lupus; Tolerance

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