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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

H. Nagafuchi¹, Y. Shimoyama, J. Kashiwakura, M. Takeno, T. Sakane, N. Suzuki

Departments of Immunology and Medicine, and ¹Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan

ABSTRACT
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.

Conclusion
SLE 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.

Key words
CD40L, B7, SLE, anti-DNA autoantibody.

Please address correspondence and reprint requests to: Dr. Noboru Suzuki, Departments of Immunology and Medicine, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan.
E-mail: n3suzuki@marianna-u.ac.jp