Secondary V(D)J rearrangements and B cell receptor-mediated down-regulation of recombination activating gene-2 expression in a murine B cell line

It has recently become clear that recombination of Ig genes is not restrict ed to B cell precursors but that secondary rearrangements can also occur un der certain conditions in phenotypically immature bone marrow and periphera l B cells. However, the nature of these cells and the regulation of seconda ry V(D)J recombination in response to B cell receptor (BCR) stimulation rem ain controversial. In the present study, we have analyzed secondary light c hain gene rearrangements and recombination activating gene (RAG) expression in the surface IgM(+), IgD(-) murine B cell line, 38C-13, which has previo usly been found to undergo kappa light chain replacement. We find that 38C- 13 cells undergo spontaneous secondary VK-JK and RS rearrangements in cultu re, with recombination occurring on both productive and nonproductive allel es, Both 38C13 cells and the Id-negative variants express the RAG genes, in dicating that the presence of RAG does not depend on activation via the 38C -13 BCR, Moreover, BCR cross-linking in 38C-13 cells leads to a rapid and r eversible down-regulation of RAG2 mRNA, Therefore, 38C-13 cells resemble pe ripheral IgM(+), IgD(-) B cells undergoing light chain gene rearrangement a nd provide a possible in vitro model for studying peripheral V(D)J recombin ation.