Selective effects of cyclophosphamide therapy on activation, proliferation, and differentiation of human B cells.
The immune function of B lymphocytes from 12 patients with nonneoplastic immune-mediated diseases receiving chronic low-dose (2 mg/kg per d) cyclophosphamide (CY) was evaluated. There was a selective and differential suppressive effect of CY therapy on the various stages of the B cell cycle including activation, proliferation, and differentiation. The proliferative responses to Staphylococcus aureus Cowan strain I (SAC) and mitogenic concentrations of anti-mu were suppressed. In contrast, B cells that have been presumably activated in vivo proliferated with a normal pattern when exposed to B cell growth factor in vitro. Chronic low-dose CY therapy also suppressed B cell differentiation. Secretion of immunoglobulin by B cells following in vitro triggering with SAC and a T cell supernatant was suppressed in CY-treated patients. Moreover, differentiation of the large in vivo-activated B cells (which do not require an in vitro activation signal) in the presence of appropriate T lymphocyte supernatant was also suppressed. This selective suppression of B cell function at multiple points in the B cell cycle may be responsible for the efficacy of CY therapy in certain antibody and immune complex-mediated diseases.
D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013211:Staphylococcus aureus
D003520:Cyclophosphamide