E2A activity is induced during B-cell activation to promote immunoglobulinclass switch recombination

The basic helix-loop-helix protein, E2A, is required for proper early B lym phopoiesis, Specifically, in E2A-deficient mice, B-cell development is bloc ked at the progenitor stage prior to the onset of immunoglobulin (Ig) V(D)J recombination. Here, we demonstrate that E2A plays an additional role duri ng peripheral B lymphopoiesis. Upon activation of primary mature B lymphocy tes, both E2A protein levels and DNA-binding activity are induced. Furtherm ore, we show that mature B cells, expressing a dominant-negative E2A antago nist, proliferate normally in response to mitogenic signaling and appropria tely express the early and late activation markers CD69, CD44, IgD and B220 , However, in the absence of E2A activity, B lymphocytes are blocked in the ir ability to express secondary Ig isotypes, We demonstrate that the defect lies at the level of DNA rearrangements between the Ig switch regions. The se data suggest that E2A is an essential target during B-cell activation an d its induction is required to promote Ig class switch recombination.