T. Kouro et al., Bruton's tyrosine kinase is required for signaling the CD79b-mediated pro-B to pre-B cell transition, INT IMMUNOL, 13(4), 2001, pp. 485-493
Formation of the pre-BCR complex is a critical check point during B cell de
velopment and induces the transition of pro-B to pre-B cells. CD79b (Ig bet
a) is a signaling component in the pre-BCR complex, since differentiation t
o the pre-B phenotype is induced by cross-linking the CD79b expressed on de
velopmentally arrested pro-B cells from recombination-activating gene (RAG)
-2-deficient mice. Bruton's tyrosine kinase (BTK) plays important roles in
B cell development. However, its molecular mechanisms In early B cell devel
opment are not fully understood. To examine whether BTK functions in CD79b-
mediated signaling for the pro-B/pre-B transition, we utilized RAG2/BTK dou
ble-knockout (DKO) mice. Pro-B cells from RAG2/BTK-DKO mice did not differe
ntiate Into pre-B cells following CD79b cross-linking, although tyrosine ph
osphorylation of cellular proteins including Erk1/2 and phospholipase C-gam
ma2 was induced in the same manner as RAG2-KO mice. BTK is phosphorylated a
fter cross-linking of CD79b on RAG2-deficient pro-B cells. These findings s
uggest that BTK-dependent pathways downstream of CD79b are critical for the
pro-B/pre-B transition and BTK-independent signaling pathways are also act
ivated via the pre-BCR complex.