RESEARCH - Systemic activation of the immune system induced aberrant BAFF and APRIL expression in B cells in patients with SLE

July 6, 2009

Arthritis Rheum. 2009 Jun 29;60(7):2083-2093.

Systemic activation of the immune system induces aberrant BAFF and

APRIL expression in B cells in patients with systemic lupus

erythematosus.

Chu VT, Enghard P, Schürer S, Steinhauser G, Rudolph B, Riemekasten G, Berek C.

Deutsches Rheuma-Forschungszentrum, Berlin, Germany.

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.

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.

PMID: 19565488

Not an MD

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