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-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 enriched for joints in D H reading frame 2 and for aberrant joints with extensive D H or J H deletions. Thus, the death of pro-B cells with failed immunoglobulin rearrangements occurs by apoptosis, and bcl-x L 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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