Protease inhibitor regulation of B-cell differentiation

Abstract Trasylol (aprotinin), also referred to as kallikrein inactivator, is known to bind and inactivate a variety of proteases, such as trypsin, chymotrypsin, cathepsin, etc., and was used in the present study as a probe for studying protease regulation of lymphoid differentiation. At concentrations of 100 to 2000 kallikrein inactivating units (KIU) per culture, this inhibitor suppressed both the primary and secondary plaque-forming cell (PFC) response of mouse spleen cells to SRBC in vitro . This suppression was not antigen specific and blocked T-independent responses as well. Suppression by Trasylol was not due to depletion effect on the antigen and its inhibitory capacity was reversible. The degree of suppression was dependent on the time of addition of Trasylol to the cultures; i.e., Trasylol added to antigen-stimulated cultures up to 48 hr after initiation of cultures was immunosuppressive whereas at 72 hr after initiation or later it did not suppress. Pretreatment of spleen cells with this inhibitor for approximately 6 hr before exposure to the antigen did not affect the immune response. When preincubated with trypsin, the suppressive activity of Trasylol was abrogated. Trasylol did not affect T helper cells or adherent cells, but it selectively suppressed the B-cell differentiation. These results suggest that protease inhibitors play an important role in immunoregulation.