Regulation of human B-cell activation, proliferation, and differentiation by soluble factors

1984 ◽  
Vol 4 (5) ◽  
pp. 337-347 ◽  
Author(s):  
Atsushi Muraguchi ◽  
John H. Kehrl ◽  
Joseph L. Butler ◽  
Anthony S. Fauci
1983 ◽  
Vol 158 (3) ◽  
pp. 690-702 ◽  
Author(s):  
A Muraguchi ◽  
J L Butler ◽  
J H Kehrl ◽  
R J Falkoff ◽  
A S Fauci

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.


1984 ◽  
Vol 78 (1) ◽  
pp. 75-96 ◽  
Author(s):  
J. H. Kehrl ◽  
A. Muraguchi ◽  
J. L. Butler ◽  
R. J. M. Falkoff ◽  
A. S. Fauci

1988 ◽  
Vol 112 (2) ◽  
pp. 251-261 ◽  
Author(s):  
Yoshiya Tanaka ◽  
Fumihiko Shirakawa ◽  
Toshiyuki Ota ◽  
Hidero Suzuki ◽  
Sumiya Eto ◽  
...  

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