In order to study the role of calcium/calmodulin kinase II (CaMKII) in T ce
lls, we generated transgenic mice expressing CaMKII gamma B* (T287D), a par
tially calcium-independent mutant of CaMKII gamma B. In these mice, the siz
e of the thymus was increased 1.5- to 2-fold, at least in part due to an in
crease in the lifespan of double-positive (DP) thymocytes. More importantly
, there was an increase in the number of T cells in the secondary lymphoid
organs that had acquired an antigen-dependent memory phenotype. These T cel
ls were bonafide memory cells as assessed by a variety of criteria. In addi
tion, T cells from wild-type mice acquired calcium-independent CaMKII activ
ity after several rounds of antigen-stimulated division. We propose that Ca
MKII controls a distinct process of activation-induced cellular differentia
tion.