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Publication : Influence of B cell antigen receptor expression level on pathways of B cell tolerance induction.

First Author  Liu X Year  2009
Journal  J Immunol Volume  182
Issue  1 Pages  398-407
PubMed ID  19109171 Mgi Jnum  J:142891
Mgi Id  MGI:3822388 Doi  10.4049/jimmunol.182.1.398
Citation  Liu X, et al. (2009) Influence of B cell antigen receptor expression level on pathways of B cell tolerance induction. J Immunol 182(1):398-407
abstractText  We have described an Ig-transgenic, autoreactive B cell clonotype that undergoes a novel tolerance pathway. Early in development this clonotype expresses average BCR levels, but these levels are progressively down-regulated as development proceeds efficiently to the mature, follicular compartment. This clonotype does not display conventional features of anergy and can be induced to undergo apoptosis and receptor editing in in vitro bone marrow cultures, but these pathways are not taken in vivo. These data suggested that autoantigen-driven down-regulation of BCR levels and, hence, avidity for autoantigen allows this clonotype to bypass conventional tolerance mechanisms. To test this idea, we enforced elevated levels of expression of BCR in this clonotype by making the transgenic Igh locus homozygous. This resulted in retarded clonotype development and L chain receptor editing in vivo. These data support a pivotal role for adaptive, autoantigen-induced adjustment of BCR expression levels in the regulation of primary B cell development and tolerance.
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