TY - JOUR
T1 - Systemic activation of the immune system induces aberrant BAFF and APRIL expression in B cells in patients with systemic lupus erythematosus
AU - Chu, Van Trung
AU - Enghard, Philipp
AU - Schürer, Stefanie
AU - Steinhauser, Gudrun
AU - Rudolph, Birgit
AU - Riemekasten, Gabriela
AU - Berek, Claudia
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/7
Y1 - 2009/7
N2 - Objective. Elevated levels of BAFF and APRIL are characteristic of patients with systemic lupus erythematosus (SLE). The reasons for enhanced cytokine production are not well understood. This study was undertaken to identify the cells responsible for the overproduction of these cytokines. Methods. BAFF expression was analyzed on peripheral blood mononuclear cells by multiparameter flow cytometry and in tissue samples by immunofluorescence staining. The levels of BAFF and APRIL mRNA were quantified in sorted B cells. In vitro cultures were used to analyze whether B cell survival and differentiation was supported by autocrine BAFF and/or APRIL. Results. Aberrant activation of B cells in patients with SLE was associated with a significant upregulation of BAFF expression in naive, memory, and plasma cells. Furthermore, strong expression of BAFF and APRIL was found in plasma cells from the lymph node, bone marrow, and kidney. The levels of BAFF and APRIL mRNA in CD19+ B cells correlated both with the titer of anti-double stranded DNA antibodies and with the SLE Disease Activity Index. In vitro experiments demonstrated that B cells released functional BAFF/APRIL upon activation. Conclusion. Our data show that B cells contribute to the enhanced levels of circulating BAFF and APRIL. The aberrant up-regulation of these cytokines may initiate a vicious circle in which enhanced levels of BAFF and APRIL act in an autocrine manner to reinforce the systemic activation of the humoral immune system.
AB - Objective. Elevated levels of BAFF and APRIL are characteristic of patients with systemic lupus erythematosus (SLE). The reasons for enhanced cytokine production are not well understood. This study was undertaken to identify the cells responsible for the overproduction of these cytokines. Methods. BAFF expression was analyzed on peripheral blood mononuclear cells by multiparameter flow cytometry and in tissue samples by immunofluorescence staining. The levels of BAFF and APRIL mRNA were quantified in sorted B cells. In vitro cultures were used to analyze whether B cell survival and differentiation was supported by autocrine BAFF and/or APRIL. Results. Aberrant activation of B cells in patients with SLE was associated with a significant upregulation of BAFF expression in naive, memory, and plasma cells. Furthermore, strong expression of BAFF and APRIL was found in plasma cells from the lymph node, bone marrow, and kidney. The levels of BAFF and APRIL mRNA in CD19+ B cells correlated both with the titer of anti-double stranded DNA antibodies and with the SLE Disease Activity Index. In vitro experiments demonstrated that B cells released functional BAFF/APRIL upon activation. Conclusion. Our data show that B cells contribute to the enhanced levels of circulating BAFF and APRIL. The aberrant up-regulation of these cytokines may initiate a vicious circle in which enhanced levels of BAFF and APRIL act in an autocrine manner to reinforce the systemic activation of the humoral immune system.
UR - http://www.scopus.com/inward/record.url?scp=67650082855&partnerID=8YFLogxK
U2 - 10.1002/art.24628
DO - 10.1002/art.24628
M3 - Journal articles
C2 - 19565488
AN - SCOPUS:67650082855
SN - 0004-3591
VL - 60
SP - 2083
EP - 2093
JO - Arthritis and Rheumatism
JF - Arthritis and Rheumatism
IS - 7
ER -