Abstracts (complete list) - Wissenschaft Online

Johannes Lutz, Werner Müller, Chander Raman, Hans-Martin Jäck
Impaired B Cell Development in the Presence of a Non-Coding
IgM mRNA
To establish allelic exclusion (AE) at the Ig heavy chain (IgH) locus VDJ recombination
of the second locus must be terminated once a productive VDJ rearrangement has been
made. Many studies have demonstrated that the suppression of further VDJ
rearrangements is mediated by the newly synthesized IgM heavy chain (•HC) through
pre-B cell receptor (pre-BCR) signals. However, it is still unclear how rearrangement of
the second IgH allele is prevented during the time required for the synthesis of the •HC
and the initiation of pre-BCR signals. Here we present evidence that a stable •HC
transcript, which reflects the presence of a productive rearrangement, can already exert
a suppressive effect on VDJ recombination in the absence of a •HC signal. B cell
development was impaired at the pro-B to pre-B cell transition with an increased
frequency of •HC-negative pro-B cells in transgenic mice expressing a non-coding •HC
transcript. This transcript contains a premature translational stop codon at position +3
and resembles rather a stable productive than an extremely unstable non-productive
•HC mRNA. Providing a productive transgenic •HC restored B cell development, which
indicated that the non-coding •HC transcript interfered with no other processes than
VDJ recombination at the IgH locus. These observations suggest a new role for •HC
transcripts by indicating the presence of a productive VDJ rearrangement and
temporarily suppressing VDJ recombination of the second IgH allele until the initiation of
signals provided by a •HC.
The work was supported in part by the project grant SFB466 and the research grant JA
968/2 from the Deutsche Forschungsgemeinschaft (DFG) to H.-M. J.