Autoreactivity in naive human fetal B cells is associated with commensal bacteria recognition

被引：27

作者：

Chen, Jeff W. ^{[1
,4
]}

Rice, Tyler A. ^{[1
]}

Bannock, Jason M. ^{[1
]}

Bielecka, Agata A. ^{[1
,5
]}

Strauss, Juliet D. ^{[1
,6
]}

Catanzaro, Jason R. ^{[1
]}

Wang, Haowei ^{[1
]}

Menard, Laurence C. ^{[1
,7
]}

Anolik, Jennifer H. ^{[2
]}

Palm, Noah W. ^{[1
]}

Meffre, Eric ^{[1
,3
]}

机构：

[1] Yale Univ, Dept Immunobiol, New Haven, CT 06511 USA

[2] Univ Rochester, Med Ctr, Div Allergy Immunol & Rheumatol, Rochester, NY 14642 USA

[3] Yale Sch Med, Sect Rheumatol Allergy & Clin Immunol, New Haven, CT 06511 USA

[4] ClearView Healthcare Partners, Newton, MA 02458 USA

[5] Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany

[6] Tulane Sch Med, New Orleans, LA 70112 USA

[7] Bristol Myers Squibb, Princeton, NJ 08540 USA

来源：

SCIENCE | 2020年 / 369卷 / 6501期

关键词：

REPERTOIRE; ANTIBODIES;

D O I：

10.1126/science.aay9733

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Restricted V(D)J recombination during fetal development was postulated to limit antibody repertoire breadth and prevent autoimmunity. However, newborn serum contains abundant autoantibodies, suggesting that B cell tolerance during gestation is not yet fully established. To investigate this apparent paradox, we evaluated the reactivities of more than 450 antibodies cloned from single B cells from human fetal liver, bone marrow, and spleen. We found that incomplete B cell tolerance in early human fetal life favored the accumulation of polyreactive B cells that bound both apoptotic cells and commensal bacteria from healthy adults. Thus, the restricted fetal preimmune repertoire contains potentially beneficial self-reactive innate-like B cell specificities that may facilitate the removal of apoptotic cells during development and shape gut microbiota assembly after birth.

引用

页码：320 / +

页数：40

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