Mechanism for pre-B cell loss in VH-mutant rabbits.

ABSTRACT: Pre-BCR signaling is a critical checkpoint in B cell development in which B-lineage cells expressing functional IgH μ-chain are selectively expanded. B cell development is delayed in mutant ali/ali rabbits because the a-allotype encoding V(H)1 gene, which is normally used in VDJ gene rearrangements in wt rabbits, is deleted, and instead, most B-lineage cells use the a-allotype encoding V(H)4 gene [V(H)4(a)], which results in a severe developmental block at the pre-B cell stage. We found that V(H)4(a)-utilizing pre-B cells exhibit reduced pre-BCR signaling and do not undergo normal expansion in vitro. Transduction of murine 38B9 pre-B cells with chimeric rabbit-VDJ mouse-Cμ encoding retroviruses showed V(H)4(a)-encoded μ-chains do not readily form signal-competent pre-BCR, thereby explainin

SUBMITTER: Robbins GR 

PROVIDER: S-EPMC3339493 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature