Mechanisms of protein A superantigen-induced signal transduction for proliferation of mouse B cell

Apart from many of the biological properties of protein A (PA) of Staphyloc occus aureus, it has been recognized recently as a B-cell superantigen. The refore, we investigated the molecular mechanisms of PA superantigen-induced mice splenic B-cell proliferation. Treatment of resting B cells with PA-ev oked cell proliferation. Binding of PA to B cells led to a cascade of signa l transduction mechanisms involving tyrosine kinase that activated phosphol ipase C, which in turn activated protein kinase C (PKC), and translocated i t from cytosol to membrane. Mitogen-activated protein (MAP) kinase has been found to be activated down-stream of PKC in this signal pathway, which ult imately caused an activation of serum-responsive factor (SRF). Inhibition a t any step of this signaling cascade could block B-cell proliferation. PA c ould also stimulate the Bcl-2 gene expression at protein level thereby supp orting the pro-proliferative effect of PA. Thus, the molecular mechanisms r elated to PA-induced B cell proliferation has been delineated in this repor t as tyrosine kinase > PLC > PKC > MAP kinase > SRF > Bcl-2. Knowledge gath ered from these observations might be of immense help to study the immune c ell proliferation as a part of immunoactivation process. Also, the developm ent of suitable inhibitors of the signaling pathway outlined here might pro vide clues as to how to abrogate pathologic antibody production in many dis ease processes. (C) 1999 Published by Elsevier Science B.V. All rights rese rved.