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Induction of Ig Light Chain Gene Rearrangement in Heavy Chain-Deficient B Cells by Activated Ras
Albert C. Shaw, Wojciech Swat, Laurie Davidson and Frederick W. Alt
Proceedings of the National Academy of Sciences of the United States of America
Vol. 96, No. 5 (Mar. 2, 1999), pp. 2239-2243
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/47044
Page Count: 5
You can always find the topics here!Topics: B lymphocytes, T lymphocytes, Gene rearrangement, Germ cells, Cellular differentiation, DNA, Spleen, Polymerase chain reaction, Cell lines, Lymph nodes
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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 JH-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/JH-deleted B cells accumulate in the periphery but continue to express markers associated with precursor B cells including RAG gene products. These peripheral Ras/JH-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.
Proceedings of the National Academy of Sciences of the United States of America © 1999 National Academy of Sciences