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 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) significantly enhanced 3H - TdR incorporation by both SLE and normal B cells (P<0.01). 3H - 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.


CONCLUSIONS
These findings indicate that signalling via CD40 plays an important role in B cell proliferation and autoantibody production in human SLE.
Harigai
M
M
Institute of Rheumatology, Tokyo Women's Medical University, Japan. vj5m-hrgi@asahi-net.or.jp
Hara
M
M
Fukasawa
C
C
Nakazawa
S
S
Kawaguchi
Y
Y
Kamatani
N
N
Kashiwazaki
S
S
D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D016022:Case-Control Studies; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D016350:Leucine Zippers / Q000235:genetics / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013936:Thymidine
D001323:Autoantibodies; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D023201:CD40 Ligand; D004247:DNA; D013936:Thymidine