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

Abstract

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 < 0:01ƒ. 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.