Themis2 lowers the threshold for B cell activation during positive selection

被引：22

作者：

Cheng, Daian ^{[1
,7
]}

Deobagkar-Lele, Mukta ^{[1
,7
]}

Zvezdova, Ekaterina ^{[2
]}

Choi, Seeyoung ^{[2
]}

Uehara, Shoji ^{[2
]}

Baup, Delphine ^{[1
]}

Bennett, Sophia C. ^{[1
]}

Bull, Katherine R. ^{[1
]}

Crockford, Tanya L. ^{[1
]}

Ferry, Helen ^{[1
]}

Warzecha, Claude ^{[2
]}

Marcellin, Marlene ^{[3
,4
]}

de Peredo, Anne Gonzalez ^{[3
,4
]}

Lesourne, Renaud ^{[5
,6
]}

Anzilotti, Consuelo ^{[1
]}

Love, Paul E. ^{[2
]}

Cornall, Richard J. ^{[1
]}

机构：

[1] Univ Oxford, Nuffield Dept Med, Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford, England

[2] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Hematopoiesis & Lymphocyte Biol, NIH, Bethesda, MD USA

[3] Inst Pharmacol & Biol Struct, Toulouse, France

[4] Univ Paul Sabatier, Univ Toulouse, CNRS, Toulouse, France

[5] Ctr Physiopathol Toulouse Purpan, Toulouse, France

[6] INSERM, U1043, CNRS, Toulouse, France

[7] Univ Paul Sabatier, Univ Toulouse, Toulouse, France

来源：

NATURE IMMUNOLOGY | 2017年 / 18卷 / 02期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

THYMOCYTE DEVELOPMENT; NEGATIVE SELECTION; LYMPHOCYTES; PROTEIN; DOWNSTREAM; PATHWAY; DETERMINES; EXPRESSION; SURVIVAL; KINASE;

D O I：

10.1038/ni.3642

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The positive and negative selection of lymphocytes by antigen is central to adaptive immunity and self-tolerance, yet how this is determined by different antigens is not completely understood. We found that thymocyte-selection-associated family member 2 (Themis2) increased the positive selection of B1 cells and germinal center B cells by self and foreign antigens. Themis2 lowered the threshold for B-cell activation by low-avidity, but not high-avidity, antigens. Themis2 constitutively bound the adaptor protein Grb2, src-kinase Lyn and signal transducer phospholipase gamma 2 (PLC-gamma 2), and increased activation of PLC-gamma 2 and its downstream pathways following B cell receptor stimulation. Our findings identify a unique function for Themis2 in differential signaling and provide insight into how B cells discriminate between antigens of different quantity and quality.

引用

页码：205 / 213

页数：9

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