Preferential expression of B7.2 (CD86), but not B7.1 (CD80), on B cells induced by CD40/CD40L interaction is essential for anti-DNA autoantibody production in patients with systemic lupus erythematosus.
OBJECTIVE
B7 (CD80/CD86) molecules are over-expressed in patients with SLE. However, it is not clear whether CD80/CD86 molecules are involved in the pathogenic autoantibody production specifically or in the polyclonal antibody production in human SLE. The present study was carried out to characterize B7 molecules on B cells in autoantibody production.


METHODS
Expression of costimulatory molecules was analyzed by RT-PCR and two-color immunofluorescence staining. Purified B cells were co-cultured with T cells in the presence of anti-costimulatory molecule antibody.


RESULTS
Excessive expression of CD86 and CD80 molecules was evident on freshly isolated B cells in patients with SLE. Normal B cells did not express CD86 molecules spontaneously and expressed it after co-culture with activated T cells. CD86 expression on normal and SLE B cells induced by the activated T cells was inhibited by the addition of anti-CD40L into the cell culture. Furthermore, CD40L expression on T cells upon activation was enhanced in SLE patients. Anti-DNA antibody production by SLE B cells in the presence of activated T cells was markedly inhibited by anti-CD86, but not anti-CD80. Anti-CD86 treatment inhibited polyclonal Ig and anti-SS-A antibody production of SLE B cells, suggesting the preferential involvement of CD86 in polyclonal antibody production.


CONCLUSIONS
SLET T cells express CD40L excessively, and the CD40/CD40L pathway is involved in the CD86 over-expression of SLE B cells; thus T cell abnormality is at least partially involved in B cell hyperactivity. Enhanced CD86 expression of B cells by CD40L is essential for polyclonal antibody production.
Nagafuchi
H
H
Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
Shimoyama
Y
Y
Kashiwakura
J
J
Takeno
M
M
Sakane
T
T
Suzuki
N
N
D000293:Adolescent; D000328:Adult; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism*; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000974:Antibodies, Antinuclear; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D023201:CD40 Ligand; D013755:Tetradecanoylphorbol Acetate