Selective effects of cyclophosphamide therapy on activation, proliferation, and differentiation of human B cells

• Published in: The Journal of clinical investigation 1987-04, Vol.79 (4), p.1082-1090
• Main Authors: LI-PING ZHU, CUPPS, T. R, WHALEN, G, FAUCI, A. S
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biological and medical sciences; Cell Differentiation - drug effects; Cell Division - drug effects; Cyclophosphamide - therapeutic use; Female; Humans; Immune System Diseases - drug therapy; Immune System Diseases - immunology; Immunomodulators; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Staphylococcus aureus
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI112922

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.