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J. Exp. Med.,
Volume 188, Number 4, August 17, 1998 735-744
By
From the Research Institute of Molecular Pathology, A-1030 Vienna, Austria
The formation of the pre-B cell receptor (BCR) corresponds to an important checkpoint in B
cell development that selects pro-B (pre-BI) cells expressing a functionally rearranged immunoglobulin µ (Igµ) heavy chain protein to undergo the transition to the pre-B (pre-BII) cell
stage. The pre-BCR contains, in addition to Igµ, the surrogate light chains 
5 and VpreB and
the signal transducing proteins Ig
and Ig
. The absence of one of these pre-BCR components is known to arrest B cell development at the pre-BI cell stage. Disruption of the Pax5
gene, which codes for the B cell-specific activator protein (BSAP), also blocks adult B lymphopoiesis at the pre-BI cell stage. Moreover, expression of the mb-1 (Ig) gene and VH-to-DHJH recombination at the IgH locus are reduced in Pax5-deficient B lymphocytes ~10- and
~50-fold, respectively. Here we demonstrate that complementation of these deficiencies in
pre-BCR components by expression of functionally rearranged Igµ and chimeric Igµ-Ig
transgenes fails to advance B cell development to the pre-BII cell stage in Pax5 (
/) mice in
contrast to RAG2 (/) mice. Furthermore, the pre-BCR is stably expressed on cultured pre-BI cells from Igµ transgenic, Pax5-deficient bone marrow, but is unable to elicit its normal signaling responses. In addition, the early developmental block is unlikely to be caused by the absence of a survival signal, as it could not be rescued by expression of a bcl2 transgene in Pax5-deficient pre-BI cells. Together, these data demonstrate that the absence of Pax5 arrests adult B
lymphopoiesis at an early developmental stage that is unresponsive to pre-BCR signaling.
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