The effect of cyclosporin A (CsA), a fungal metabolite with immunosuppressive properties, on the induction of human B cell proliferation and differentiation, has been described. CsA had a selective inhibitory effect on the activation phase of the cell cycle vs. the proliferation phase following preactivation of the cells. Cell enlargement and RNA synthesis of small resting B cells triggered by anti-mu were inhibited by addition of CsA (5-500 ng/ml). The inhibitory effect of CsA was found only when the drug was added within 24 h of initiation of culture. In marked contrast, once small B cells were activated by anti-mu, the resulting large, activated B cells could be induced to initiate DNA synthesis by incubation with B cell growth factor (BCGF), and addition of CsA (1-1,000 ng/ml) to the culture did not suppress this BCGF-induced B cell proliferation. Addition of CsA to cultures of B cells which had been preactivated with Staphylococcus aureus Cowan strain I (SAC) and were already proliferating did not suppress B cell differentiation factor (BCDF)-induced differentiation of these cells. Thus, these data indicate that CsA can be used as a pharmacologic tool to dissect out human B cell responses into two distinct steps: (a) the initial activation step induced by anti-Ig, which is characterized by cell enlargement, RNA synthesis, and expression of receptors for BCGF; and (b) the proliferative step induced by BCGF in these preactivated B cells that undergo DNA synthesis and can then go on to differentiate in the presence of BCDF. In this regard, CsA selectively suppresses an early step of human B cell activation and has little inhibitory effect on the subsequent factor-dependent proliferation and differentiation.
Selective suppression of an early step in human B cell activation by cyclosporin A.
A Muraguchi, J L Butler, J H Kehrl, R J Falkoff, A S Fauci; Selective suppression of an early step in human B cell activation by cyclosporin A.. J Exp Med 1 September 1983; 158 (3): 690–702. doi: https://doi.org/10.1084/jem.158.3.690
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