FREQUENT ABERRANT IMMUNOGLOBULIN GENE REARRANGEMENTS IN PRO-B CELLS REVEALED BY A BCL-X(L) TRANSGENE

During B lymphocyte development, pro-B cells that fail to rearrange an immunoglobulin heavy (IgH) chain allele productively are thought to u ndergo developmental arrest and death, but because these cells are sho rt-lived in vivo they are not well characterized. Transgenic mice expr essing the apoptosis regulatory gene bcl-x(L) in the B lineage develop ed large expansions of pro-B cells in bone marrow. V(D)J rearrangement s 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 ap optosis, and bcl-x(L) can deliver a strong survival signal at the pro- B stage. This analysis also demonstrates that immunoglobulin gene rear rangement is less precise than previously appreciated.