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

Objective: To investigate the immunopathological significance of CD40/CD40 ligand system for B cell hyperactivation in SLE patients, the expression an d the function of CD40 on B cells were compared with those of normal contro ls. Methods: Expression of CD40 was evaluated by flow cytometry. DNA synthesis of B cells were measured by H-3 - TdR incorporation. Antibody production wa s assessed by ELISA. Results: There was no significant difference between SLE and normal control s in CD40 expression on peripheral blood B cells. Recombinant CD40 ligand-l eucine zipper fusion protein (CD40L-LZ) significantly enhanced 3H - TdR inc orporation by both SLE and normal B cells (P < 0.01). H-3 - TdR incorporati on 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 c ontrols. Active SLE B cells spontaneously produced significantly larger amo unts of total IgG than normal B cells (P < 0.05). CD40L-LZ significantly in creased the production of total IgG by SLE B cells (P < 0.05), but not by n ormal B cells. Active SLE B cells spontaneously produced IgG anti-dsDNA and ISG anti-ssDNA antibodies. CD40L-LZ significantly increased the production of these autoantibodies by SLE B cells (P < 0.05). B cells from normal con trols do not produce these autoantibodies spontaneously nor in response to CD40L-LZ. Conclusion: These findings indicate that signalling via CD40 plays an impor tant role in B cell proliferation and autoantibody production in human SLE.