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Responsiveness of peripheral blood B cells to recombinant CD40 ligand in patients with systemic lupus erythematosus

Institute of Rheumatology, Tokyo Women's Medical University, 10–22 Kawada-cho, Shinjukuku, Tokyo 162-0054, Japan; vj5m-hrgi{at}asahi-net.or.jp

M Hara

C Fukasawa

S Nakazawa

Y Kawaguchi

N Kamatani

S Kashiwazaki

Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan

Objective: To investigate the immunopathological significance of CD40=CD40 ligand system for B cell hyperactivation in SLE patients, the expression and the function of CD40 on B cells were compared with those of normal controls.

Methods: Expression of CD40 was evaluated by flow cytometry. DNA synthesis of B cells were measured by ³H–TdR incorporation. Antibody production was assessed by ELISA.

Results: There was no significant difference between SLE and normal controls in CD40 expression on peripheral blood B cells. Recombinant CD40 ligand-leucine zipper fusion protein (CD40L-LZ) ³significantly enhanced 3H ÿ TdR incorporation by both SLE and normal B cells–P < 0:01. H ÿ TdR incorporation of SLE B cells without stimuli (P < 0:001) and with CD40L-LZ stimulation (p < 0:05) were significantly lower in SLE patients compared with normal controls. Active SLE B cells spontaneously produced significantly larger amounts of total IgG than normal B cells (P < 0:05). CD40L-LZ significantly increased the production of total IgG by SLE B cells (P < 0:05), but not by normal B cells. Active SLE B cells spontaneously produced IgG anti-dsDNA and IgG anti-ssDNA antibodies. CD40L-LZ significantly increased the production of these autoantibodies by SLE B cells (P < 0:05). B cells from normal controls do not produce these autoantibodies spontaneously nor in response to CD40L-LZ.

Conclusion: These findings indicate that signalling via CD40 plays an important role in B cell proliferation and autoantibody production in human SLE.

Key Words: systemic lupus erythematosus • B lymphocyte • CD40 • CD40 ligand • anti-DNA antibody

Lupus, Vol. 8, No. 3, 227-233 (1999)
DOI: 10.1191/096120399678847678


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