Characterization of B cell growth in systemic lupus erythematosus. Effects of recombinant 12-kDa B cell growth factor, interleukin 4 and transforming growth factor-beta.
B cells from systemic lupus erythematosus (SLE) patients have been shown to be hyperactive as measured by proliferation and immunoglobulin production. We find that B cells from 6 of 13 SLE patients, in the absence of prior activation, respond two to three times better to recombinant 12-kDa B cell growth factor (BCGF) than do normal or rheumatoid arthritis B cells (p less than 0.005). B cells from normally responsive SLE patients require an anti-mu antibody activation step to generate similar proliferative signal in response to r12-kDa-BCGF. There are no clinical or serological parameters that distinguish these hyperresponsive SLE patients from the normally responsive SLE patients. The combination of r12-kDa-BCGF and interleukin 4 (IL4) gives an enhanced response with both normal and SLE B cells. Transforming growth factor type beta (TGF-beta) suppresses the response to r12-kDa-BCGF in a dose-dependent fashion using B cells from both healthy donors and SLE patients. We conclude that peripheral blood B cells are in an activated state (as detected by response to 12-kDa-BCGF) in approximately 50% of SLE patients. These B cells respond normally to regulation by IL4 and TGF-beta. A therapeutic approach aimed at reducing the B cell hyperactivity in SLE would involve suppressing the effects of 12-kDa-BCGF and IL4 while at the same time enhancing the effects of TGF-beta.
Flescher
E
E
Clinical Immunology Section, Audie L. Murphy Memorial Veterans Hospital, San Antonio, TX.
Fossum
D
D
Ballester
A
A
Maizel
A
A
Sharma
S
S
Talal
N
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007376:Interleukin-2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D015847:Interleukin-4