Gm. Dingjan et al., Bruton's tyrosine kinase regulates the activation of gene rearrangements at the lambda light chain locus in precursor B cells in the mouse, J EXP MED, 193(10), 2001, pp. 1169-1178
Bruton's tyrosine kinase (Btk) is a nonreceptor tyrosine kinase involved in
precursor B (pre-B) cell receptor signaling. Here we demonstrate that Btk-
deficient mice have an similar to 50% reduction in the frequency of immunog
lobulin (Ig) h light chain expression, already at the immature B cell stage
in the bone marrow. Conversely, transgenic mice expressing the activated m
utant Btk(E41K) showed increased lambda usage. As the kappa/lambda ratio is
dependent on (a) the level and kinetics of K and h locus activation, (b) t
he life span of pre-B cells, and (c) the extent of receptor editing, we ana
lyzed the role of Btk in these processes. Enforced expression of the Bcl-2
apoptosis inhibitor did not alter the Btk dependence of X usage. Crossing 3
-83 mu delta autoantibody transgenic mice into Btk-deticient mice showed th
at Btk is not essential for receptor editing. Also, Btk-deficient surface I
g(+) B cells that were generated in vitro in interleukin 7-driven bone marr
ow cultures manifested reduced h usage. An intrinsic defect in X locus reco
mbination was further supported by the finding in Btk-deficient mice of red
uced h usage in the fraction of pre-B cells that express light chains in th
eir cytoplasm. These results implicate Btk in the regulation of the activat
ion of the X locus for V(D)J recombination in pre-B cells.