Defective Expression and Function of the Leukocyte Associated Ig-like Receptor 1 in B Lymphocytes from Systemic Lupus Erythematosus Patients

Autor: Ottavia Magnani, Alessandro Poggi, Paolo Canevali, Edoardo Rossi, Barbara Maria Colombo, Maria Raffaella Zocchi, Francesco Puppo
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Genetics and Molecular Biology (all)
Male
Transcription
Genetic
Lymphocyte
Fluorescent Antibody Technique
Lymphocyte Activation
Biochemistry
Scleroderma
Mixed connective tissue disease
Immunologic
Receptors
Medicine
Lupus Erythematosus
Systemic
Receptors
Immunologic
skin and connective tissue diseases
Cells
Cultured
B-Lymphocytes
Multidisciplinary
Cultured
biology
Mesenchymal Stromal Cells
Medicine (all)
NF-kappa B
Middle Aged
Adult
Aged
Calcium
Case-Control Studies
Collagen
Female
Humans
Immunoglobulin G
Mixed Connective Tissue Disease
Protein Transport
Scleroderma
Systemic
Young Adult
Agricultural and Biological Sciences (all)
Biochemistry
Genetics and Molecular Biology (all)
medicine.anatomical_structure
Antibody
Transcription
Research Article
Science
Cells
Immune Cells
B-cell receptor
Immunology
Autoimmune Diseases
Genetic
Biology
B cell
Lupus Erythematosus
business.industry
Pokeweed mitogen
Mesenchymal stem cell
Systemic
Immunity
Mesenchymal Stem Cells
medicine.disease
biology.protein
Clinical Immunology
Bone marrow
business
Zdroj: PLoS ONE
PLoS ONE, Vol 7, Iss 2, p e31903 (2012)
ISSN: 1932-6203
Popis: Systemic lupus erythematosus (SLE) is characterized by the production of a wide array of autoantibodies and dysregulation of B cell function. The leukocyte associated Immunoglobulin (Ig)-like receptor (LAIR)1 is a transmembrane molecule belonging to Ig superfamily which binds to different types of collagen. Herein, we have determined the expression and function of LAIR1 on B lymphocyte from SLE patients. LAIR1 expression in peripheral blood B lymphocytes from 54 SLE, 24 mixed connective tissue disease (MCTD), 20 systemic sclerosis (SSc) patients, 14 rheumatoid arthritis (RA) and 40 sex and age matched healthy donors (HD) have been analyzed by immunofluorescence. The effect of LAIR1 ligation by specific monoclonal antibodies, collagen or collagen producing mesenchymal stromal cells from reactive lymph nodes or bone marrow on Ig production by pokeweed mitogen and B cell receptor (BCR)-mediated NF-kB activation was assessed by ELISA and TransAM assay. The percentage of CD20(+) B lymphocytes lacking or showing reduced expression of LAIR1 was markedly increased in SLE and MCTD but not in SSc or RA patients compared to HD. The downregulation of LAIR1 expression was not dependent on corticosteroid therapy. Interestingly, LAIR1 engagement by collagen or collagen-producing mesenchymal stromal cells in SLE patients with low LAIR1 expression on B cells delivered a lower inhibiting signal on Ig production. In addition, NF-kB p65 subunit activation upon BCR and LAIR1 co-engagement was less inhibited in SLE patients than in HD. Our findings indicate defective LAIR1 expression and function in SLE B lymphocytes, possible contributing to an altered control of B lymphocytes behavior.
Databáze: OpenAIRE
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