|
||
Original Article |
Light Chain Locus in Precursor B Cells in the Mouse
hendriks{at}immu.fgg.eur.nl
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
50% reduction in the frequency of immunoglobulin (Ig)
light chain expression, already at the immature B cell stage in the bone marrow. Conversely, transgenic mice expressing the activated mutant BtkE41K showed increased
usage. As the
/
ratio is dependent on (a) the level and kinetics of
and
locus activation, (b) the life span of pre-B cells, and (c) the extent of receptor editing, we analyzed the role of Btk in these processes. Enforced expression of the Bcl-2 apoptosis inhibitor did not alter the Btk dependence of
usage. Crossing 3-83µ
autoantibody transgenic mice into Btk-deficient mice showed that Btk is not essential for receptor editing. Also, Btk-deficient surface Ig+ B cells that were generated in vitro in interleukin 7-driven bone marrow cultures manifested reduced
usage. An intrinsic defect in
locus recombination was further supported by the finding in Btk-deficient mice of reduced
usage in the fraction of pre-B cells that express light chains in their cytoplasm. These results implicate Btk in the regulation of the activation of the
locus for V(D)J recombination in pre-B cells.
Key Words: Btk B lymphocytes Ig L chain receptor editing V(D)J rearrangements
© 2001 The Rockefeller University Press
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Facebook
Reddit
Technorati
Twitter What's this?
| TABLE OF CONTENTS |
|