[PDF][PDF] Frequent aberrant immunoglobulin gene rearrangements in pro-B cells revealed by a bcl-xL transgene

W Fang, DL Mueller, CA Pennell, JJ Rivard, YS Li… - Immunity, 1996 - cell.com
W Fang, DL Mueller, CA Pennell, JJ Rivard, YS Li, RR Hardy, MS Schlissel, TW Behrens
Immunity, 1996cell.com
During B lymphocyte development, pro-B cells that fail to rearrange an immunoglobulin
heavy (IgH) chain allele productively are thought to undergo developmental arrest and
death, but because these cells are short-lived in vivo they are not well characterized.
Transgenic mice expressing the apoptosis regulatory gene bcl-x L in the B lineage
developed large expansions of pro-B cells in bone marrow. V (D) J rearrangements in the
expanded population were nearly all nonproductive, and DJ H rearrangements were …
Abstract
During B lymphocyte development, pro-B cells that fail to rearrange an immunoglobulin heavy (IgH) chain allele productively are thought to undergo developmental arrest and death, but because these cells are short-lived in vivo they are not well characterized. Transgenic mice expressing the apoptosis regulatory gene bcl-xL in the B lineage developed large expansions of pro-B cells in bone marrow. V(D)J rearrangements in the expanded population were nearly all nonproductive, and DJH rearrangements were enriched for joints in DH reading frame 2 and for aberrant joints with extensive DH or JH deletions. Thus, the death of pro-B cells with failed immunoglobulin rearrangements occurs by apoptosis, and bcl-xL can deliver a strong survival signal at the pro-B stage. This analysis also demonstrates that immunoglobulin gene rearrangement is less precise than previously appreciated.
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