Down-regulation of RAG1 and RAG2 gene expression in preB cells after functional immunoglobulin heavy chain rearrangement

U Grawunder, TMJ Leu, DG Schatz, A Werner… - Immunity, 1995 - cell.com
U Grawunder, TMJ Leu, DG Schatz, A Werner, AG Rolink, F Melchers, TH Winkler
Immunity, 1995cell.com
Two waves of immunoglobulin gene rearrangements, first of the heavy, then of the light
chain gene loci form functional immunoglobulin genes during B cell development. In mouse
bone marrow the differential surface expression of 8220 (CD45R), c-kit, CD25 and surrogate
light chain as well as the cell cycle status allows FACS separation of the cells in which these
two waves of rearrangements occur. The gene products of two recombination activating
genes, RAG7 and RAG2 are crucial for this rearrangement process. Here, we show that the …
Summary
Two waves of immunoglobulin gene rearrangements, first of the heavy, then of the light chain gene loci form functional immunoglobulin genes during B cell development. In mouse bone marrow the differential surface expression of 8220 (CD45R), c-kit, CD25 and surrogate light chain as well as the cell cycle status allows FACS separation of the cells in which these two waves of rearrangements occur. The gene products of two recombination activating genes, RAG7 and RAG2 are crucial for this rearrangement process. Here, we show that the expression of the RAG genes is twice up-and down-regulated, at the transcriptional level for RAG7 and RAGP, and at the postranscriptional level for RAG2 protein. Expression levels are high in D-, JH and VH-+ DJH rearranging proB and preB-I cells, low in preB cells expressing the preB cell receptor on the cell surface, and high again in VL-, JL rearranging small preB-II cells. In immature B cells expressing on the cell surface RAG1 and RAG2 mRNA is down-regulated, whereas RAG2 protein levels are maintained. Downregulation of RAG7 and RAG2 gene expression after productive rearrangement at one heavy chain allele might be part of the mechanisms that prevent further rearrangements at the other allele.
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