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*
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037; and
Department of Microbiology and Immunology, and Program in Molecular Biology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153
Ig gene rearrangements could generate
VH-D-JH joining sequences that interfere with
the correct folding of a µ-chain, and thus, its capability to pair
with IgL chains. Surrogate light (SL) chain might be the ideal molecule
to test the capacity of a µ-chain to pair with a L chain early in
development, in that only pre-B cells that assemble a membrane µ-SL
complex would be permitted to expand and further differentiate. We have
previously identified two SL chain nonpairing
VH81X-µ-chains with distinct
VH-D-JH joining regions. Here, we show that one
of these VH81X-µ-chains does not rescue B cell
development in JH knock-out mice, because flow cytometric
analysis of bone marrow cells from VH81X-µ transgenic
JH knock-out mice revealed normal numbers of pro-B cells,
but essentially no pre-B and surface IgM+ B cells.
Immunoprecipitation analysis of transfected pre-B and hybridoma lines
revealed that the same µ-chain fails to pair not only with SL chain
but also with four distinct 
L chains. These findings demonstrate
that early pre-B cells are selected for maturation on the basis of the
structure of a µ-chain, in particular its
VH-D-JH joining or CDR3 sequence, and that one
mechanism for this selection is the capacity of a µ-chain to assemble
with SL chain. Therefore, we propose a new function of SL chain in
early B cell development: SL chain is part of a quality control
mechanism that tests a µ-chain for its ability to pair with
conventional L chains.
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