Suppression of B cell activation by cyclosporin A, FK506 and rapamycin

✍ Scribed by Linda S. Wicker; Robert C. Boltz Jr.; Victoria Matt; Elizabeth A. Nichols; Laurence B. Peterson; Nolan H. Sigal

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 722 KB
• Volume: 20
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830201017

✦ Synopsis

Abstract

The effects of the immunosuppressants cyclosporin A (CsA), FK506 and rapamycin have been compared using murine B cells activated with a variety of mitogens. FK506 is a macrolide antibiotic that has been recently shown to inhibit T cell activation by a mechanism that appears similar to that of CsA. Rapamycin is a macrolide structurally related to FK506 whose mechanism of T cell suppression appears to be distinct from that of FK506 and CsA. While CsA and FK506 were found to preferentially inhibit B cell activation caused by stimuli which induce a rise in intracellular calcium, rapamycin partially inhibited activation by all stimuli tested, including those which are not associated with a calcium flux. All three compounds were found to inhibit cell cycle progression within the G~1~ phase; however, the rapamycin‐sensitive event within G~1~ was completed earlier than the G~1~ events inhibited by CsA and FK506. In addition, inhibition of anti‐IgM‐activated B cells with CsA and FK506, but not with rapamycin, resulted in cell death. These data suggest that although CsA, FK506 and rapamycin are all inhibitors of B cell activation, the inhibitory activity of rapamycin can be clearly distinguished from that of CsA and FK506.

Although the suppressive effects of CsA and FK506 on B cell proliferation were nearly identical in this study, their biological activities were distinguishable since FK506, but not CsA, could antagonize rapamycin‐mediated suppression.