Expression of B-cell activating factor of the tumour necrosis factor family (BAFF) in T cells in active systemic lupus erythematosus: the role of BAFF in T cell-dependent B cell pathogenic autoantibody production.
OBJECTIVE
To determine whether B cell activating factor of the tumour necrosis factor family (BAFF) is involved in T cell-dependent B cell pathogenic autoantibody production in systemic lupus erythematosus (SLE).


METHODS
Peripheral blood mononuclear cells (PBMCs) from 23 SLE patients were analysed by flow cytometry to examine the intracellular expression of BAFF in CD4+ and CD8+ T cells and the surface expression of BAFF-receptor (R) and TACI on CD20+ B cells. Moreover, peripheral blood was used to determine the level of BAFF messenger RNA (mRNA) in CD4+ and CD8+ T cells and the level of BAFF-R mRNA in CD20+ B cells. Blocking of BAFF function with TACI-Ig measured anti-double-stranded DNA (dsDNA) antibodies by enzyme-linked immunosorbent assay (ELISA).


RESULTS
CD4+ and CD8+ T cells from patients with active SLE expressed intracellular BAFF whereas those from normal subjects did not. BAFF-R and TACI were expressed on B cells from both normal controls and patients with active SLE and there was no significant difference. CD4+ and CD8+ T cells from SLE patients expressed BAFF mRNA whereas those from normal controls did not. Expression of BAFF-R mRNA in CD20+ B cells showed no significant difference between SLE patients and normal controls. TACI-Ig suppressed spontaneous in vitro T cell-dependent B cell anti-dsDNA antibodies production on active SLE with kidney involvement.


CONCLUSIONS
BAFF may play a pathogenic role in SLE by stimulating T cell-dependent B cell autoantibodies production. Blockade of BAFF is a promising therapeutic approach for SLE especially in patients with kidney involvement.
Morimoto
S
S
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan. morimoto@med.juntendo.ac.jp
Nakano
S
S
Watanabe
T
T
Tamayama
Y
Y
Mitsuo
A
A
Nakiri
Y
Y
Suzuki
J
J
Nozawa
K
K
Amano
H
H
Tokano
Y
Y
Kobata
T
T
Takasaki
Y
Y
D000208:Acute Disease; D000974:Antibodies, Antinuclear / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008181:Lupus Nephritis / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000737:chemistry* / Q000276:immunology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000494:pharmacology
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D012333:RNA, Messenger; C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D004247:DNA