Systemic activation of the immune system induces aberrant BAFF and APRIL expression in B cells in patients with systemic lupus erythematosus.
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 up-regulation 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.


CONCLUSIONS
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.
Chu
Van Trung
VT
Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Enghard
Philipp
P
Schürer
Stefanie
S
Steinhauser
Gudrun
G
Rudolph
Birgit
B
Riemekasten
Gabriela
G
Berek
Claudia
C
D000974:Antibodies, Antinuclear / Q000378:metabolism; D053264:B-Cell Activating Factor / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007107:Immune System / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism* / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism*
D000974:Antibodies, Antinuclear; D053264:B-Cell Activating Factor; D012333:RNA, Messenger; C505719:TNFSF13B protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13