Cystic fibrosis patients' B-lymphocyte response is resistant to the in vitro enhancing effect of corticosteroids.
Cystic fibrosis is associated with an cAMP-regulated channel defect, which has been evidenced in many cell types including B lymphocytes. To document a B-cell dysfunction potentially related to this defect, we studied the in vitro IgG production by lymphocytes from 11 cystic fibrosis patients. B lymphocytes were co-cultured with autologous monocytes and stimulated with Staphylococcus aureus Cowan or with Nocardia-delipidated cell mitogen in the presence of low concentrations of IL2. Cystic fibrosis patients' cells produced amounts of IgG comparable with that of normal and control patients' cells. However, dexamethasone (10(-7) mol l-1) had no effect on the response of cystic fibrosis patients' cells, whereas it enhanced that of the latter two groups. This resistance of cystic fibrosis cells was true with concentrations of dexamethasone up to 10(-6) mol l-1, whereas this agent induced a dose-related enhancement from 10(-8) to 10(-6) mol l-1 in cultures of normal cells. Co-culture experiments showed that cystic fibrosis B lymphocytes themselves are resistant to the effect of dexamethasone. In contrast dexamethasone normally suppressed the anti-CD3 antibody-induced response of cystic fibrosis T cells in the presence of IL2 and the IL1 alpha- or beta-induced collagenase production of cystic fibrosis fibroblast cell lines. Thus cystic fibrosis B lymphocytes exhibit a selective defect which may interfere with the normal interactions between the hormonal and immune systems and may participate in the sensitivity of cystic fibrosis patients to bacterial bronchopulmonary infections.
Emilie
D
D
INSERM U 131, Clamart, France.
Crevon
M C
MC
Chicheportiche
R
R
Auffredou
M T
MT
Barot-Ciorbaru
R
R
Lenoir
G
G
Dayer
J M
JM
Galanaud
P
P
D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000276:immunology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D003012:Microbial Collagenase / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D007074:Immunoglobulin G; D003907:Dexamethasone; D003012:Microbial Collagenase