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* Walter and Eliza Hall Institute of Medical Research, and
Ludwig Institute for Cancer Research, Melbourne Tumor Biology Branch, P. O. Royal Melbourne Hospital, Victoria, Australia
The cell surface glycoprotein CD19 and the Src-related protein
tyrosine kinase Lyn are key mediators of, respectively, positive and
negative signaling in B cells. Despite the apparent opposition of their
regulatory functions, a recent model of the biochemical events after B
cell receptor (BCR) ligation intimately links the activation of Lyn and
CD19. We examined the biochemical consequences of BCR ligation in mouse
B cells lacking either Lyn or CD19 for evidence of interaction or
codependence. In contrast to published results, we found CD19
phosphorylation after BCR ligation to be unaffected by the absence of
Lyn, yet dependent on Src family protein tyrosine kinases as it was
inhibited fully by PP2, an Src family-specific inhibitor. Consistent
with normal CD19 phosphorylation in lyn-/-
B cells, the recruitment of phosphoinositide-3 kinase to CD19 and the
ability of CD19 to enhance both intracellular calcium flux and
extracellular signal-regulated kinase 1/2 activation after coligation
with the BCRs were intact in the absence of Lyn. Similarly, unique
functions of Lyn were found to be independent of CD19.
CD19-/- B cells were normal for increased Lyn kinase
activity after BCR ligation, inhibition of BCR-mediated calcium flux
after CD22 coligation, and inhibition of extracellular signal-regulated
kinase phosporylation after Fc
RIIB coligation. Collectively, these
data show that the unique functions of Lyn do not require CD19 and that
the signal amplification mediated by CD19 is independent of Lyn. We
conclude that the roles of Lyn and CD19 after BCR ligation are
independent and opposing, one being primarily inhibitory and the other
stimulatory.
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