FcγRIIB signals inhibit BLyS signaling and BCR-mediated BLyS receptor up-regulation

被引：30

作者：

Crowley, Jenni E. ^{[1
]}

Stadanlick, Jason E. ^{[1
]}

Cambier, John C. ^{[2
]}

Cancro, Michael P. ^{[1
]}

机构：

[1] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[2] Univ Colorado, Denver Sch Med & Natl Jewish Hlth, Dept Immunol, Denver, CO 80202 USA

来源：

BLOOD | 2009年 / 113卷 / 07期

关键词：

B-LYMPHOCYTE STIMULATOR; NECROSIS-FACTOR FAMILY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CUTTING EDGE; NEGATIVE REGULATION; AUTOIMMUNE-DISEASE; HUMORAL IMMUNITY; CELL DEVELOPMENT; SURVIVAL FACTOR; DEFICIENT MICE;

D O I：

10.1182/blood-2008-02-138651

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

These studies investigate how interactions between the BCR and Fc gamma RIIB affect B lymphocyte stimulator ( BLyS) receptor expression and signaling. Previous studies showed that BCR ligation up-regulates BLyS binding capacity in mature B cells, reflecting increased BLyS receptor levels. Here we show that Fc gamma RIIB coaggregation dampens BCR-induced BLyS receptor up-regulation. This cross-regulation requires BCR and Fc gamma RIIB coligation, and optimal action relies on the Src-homology-2 (SH2) containing inositol 5 phosphase-1 (SHIP1). Subsequent to Fc gamma RIIB/BCR coaggregation, the survival promoting actions of BLyS are attenuated, reflecting reduced BLyS receptor signaling capacity in terms of Pim 2 maintenance, noncanonical NF-kappa B activation, and Bcl-xL levels. These findings link the negative regulatory functions of Fc gamma RIIB with BLyS-mediated B-cell survival. ( Blood. 2009; 113: 1464-1473)

引用

页码：1464 / 1473

页数：10

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