Mechanisms of Immunological Self-Tolerance and Autoimmunity 
singly or in combination. These studies have be- 
gun to reveal a complex pattern of crosstalk be- 
tween IgM and IgD receptors, which may help in 
dissecting the immediate events within the B cell 
that determine whether it is activated or rendered 
tolerant. 
Once antigen binds to receptors on the B cell 
surface, the choice between being provoked into 
attack or becoming tolerant is ultimately deter- 
mined by biochemical events inside each recep- 
tor-bearing cell. By studying the responses of tol- 
erant and nontolerant B lymphocytes isolated 
from transgenic mice and maintained in tissue 
culture, we are beginning to identify some of the 
key changes involved in silencing the B cells that 
are reactive to self. These include both modula- 
tion of the antigen receptors themselves and 
blocking of the cells' ability to diflf^erentiate into 
antibody secretors. Transgenic mouse technol- 
ogy, allowing genetic dissection of signaling cir- 
cuits within the B cells, together with standard 
techniques of biochemical analysis, should en- 
able us first to gain an understanding of the nor- 
mal controls exerted on B lymphocytes and even- 
tually to illuminate the breakdown of these 
controls in autoimmunity. 
176 
