Induction of Ig light chain gene rearrangement in heavy chain-deficient B cells by activated ras

Albert C. Shaw, Wojciech Swat, Laurie Davidson, Frederick W. Alt

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


During B cell development, rearrangement and expression of Ig heavy chain (HC) genes promote development and expansion of pre-B cells accompanied by the onset of Ig light chain (LC) variable region gene assembly. To elucidate the signaling pathways that control these events, we have tested the ability of activated Ras expression to promote B cell differentiation to the stage of LC gene rearrangement in the absence of Ig HC gene expression. For this purpose, we introduced an activated Ras expression construct into J(H)deleted embryonic stem cells that lack the ability to assemble HC variable region genes and assayed differentiation potential by recombination activating gene (RAG) 2-deficient blastocyst complementation. We found that activated Ras expression induces the progression of B lineage cells beyond the developmental checkpoint ordinarily controlled by μ HC. Such RaS/J(H)- deleted B cells accumulate in the periphery but continue to express markers associated with precursor B cells including RAG gene products. These peripheral Ras/J(H)deleted B cell populations show extensive Ig LC gene rearrangement but maintain an extent of κ LC gene rearrangement and a preference for κ over λ LC gene rearrangement similar to that of wild-type B cells. We discuss these findings in the context of potential mechanisms that may regulate Ig LC gene rearrangement.

Original languageEnglish
Pages (from-to)2239-2243
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
StatePublished - Mar 2 1999


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