Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) acts as a regulator of B-cell development, B-cell antigen receptor (BCR)-mediated activation, and autoimmune disease

被引：85

作者：

Wilkinson, R ^{[1
]}

Lyons, AB ^{[1
]}

Roberts, D ^{[1
]}

Wong, MX ^{[1
]}

Bartley, PA ^{[1
]}

Jackson, DE ^{[1
]}

机构：

[1] Inst Med & Vet Sci, Hanson Inst, Div Haematol, Adelaide, SA 5000, Australia

来源：

BLOOD | 2002年 / 100卷 / 01期

关键词：

D O I：

10.1182/blood-2002-01-0027

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is an immunoglobulin-immunoreceptor tyrosine-based inhibitory motif (Ig-ITIM) superfamily member that recruits and activates protein-tyrosine phosphatases, SHP-1 and SHP-2, through its intrinsic ITIMs. PECAM-1-deficient (PECAM-1(-/-)) mice exhibit a hyperresponsive B-cell phenotype, increased numbers of B-1 cells, reduced B-2 cells, and develop autoantibodies. In the periphery, there are reduced mature recirculating B-2 cells and increased B-1a cells within the peritoneal cavity. In addition, PECAM-1(-/-) B cells display hyperproliferative responses to lipopolysaccharide and anti-IgM stimulation and showed enhanced kinetics in their intracellular Ca++ response following IgM cross-linking. PECAM-1(-/-) mice showed increased serum levels of IgM with elevated IgG isotypes and IgA antidinitrophenol antibody in response to the T-independent antigen, dinitrophenol-Ficoll. Finally, PECAM-1(-/-) mice developed antinuclear antibodies and lupuslike autoimmune disease with age.

引用

页码：184 / 193

页数：10

共 42 条

[21] A 13-AMINO-ACID MOTIF IN THE CYTOPLASMIC DOMAIN OF FC-GAMMA-RIIB MODULATES B-CELL RECEPTOR SIGNALING [J].

MUTA, T ;

KUROSAKI, T ;

MISULOVIN, Z ;

SANCHEZ, M ;

NUSSENZWEIG, MC ;

RAVETCH, JV .

NATURE, 1994, 368 (6466) :70-73

[22] Inhibition of antigen-receptor signaling by platelet endothelial cell adhesion molecule-1 (CD31) requires functional ITIMs, SHP-2, and p56lck [J].

Newman, DK ;

Hamilton, C ;

Newman, PJ .

BLOOD, 2001, 97 (08) :2351-2357

[23] Switched at birth: a new family for PECAM-1 [J].

Newman, PJ .

JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (01) :5-9

[24]

Newton-Nash DK, 1999, J IMMUNOL, V163, P682

[25] Immunological studies on PD-1-deficient mice: implication of PD-1 as a negative regulator for B cell responses [J].

Nishimura, H ;

Minato, N ;

Nakano, T ;

Honjo, T .

INTERNATIONAL IMMUNOLOGY, 1998, 10 (10) :1563-1572

[26] Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor [J].

Nishimura, H ;

Nose, M ;

Hiai, H ;

Minato, N ;

Honjo, T .

IMMUNITY, 1999, 11 (02) :141-151

[27] Deficiency in CD22, a B cell-specific inhibitory receptor, is sufficient to predispose to development of high affinity autoantibodies [J].

O'Keefe, TL ;

Williams, GT ;

Batista, FD ;

Neuberger, MS .

JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (08) :1307-1313

[28] Hyperresponsive B cells in CD22-Deficient mice [J].

OKeefe, TL ;

Williams, GT ;

Davies, SL ;

Neuberger, MS .

SCIENCE, 1996, 274 (5288) :798-801

[29] Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling [J].

Ono, M ;

Okada, H ;

Bolland, S ;

Yanagi, S ;

Kurosaki, T ;

Ravetch, JV .

CELL, 1997, 90 (02) :293-301

[30] CD22 regulates thymus-independent responses and the lifespan of B cells [J].

Otipoby, KL ;

Andersson, KB ;

Draves, KE ;

Klaus, SJ ;

Farr, AG ;

Kerner, JD ;

Perlmutter, RM ;

Law, CL ;

Clark, EA .

NATURE, 1996, 384 (6610) :634-637

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