Transcription Factor Ets1, but Not the Closely Related Factor Ets2, Inhibits Antibody-Secreting Cell Differentiation

B cell differentiation into antibody-secreting cells (ASCs) is a tightly regulated process under the control of multiple transcrip-tion factors. One such transcription factor, Ets1, blocks the transition of B cells to ASCs via two separate activities: (i) stimulat-ing the expression of target genes that promote B cell identity and (ii) interfering with the functional activity of the transcription factor Blimp1. Ets1 is a member of a multigene family, several members of which are expressed within the B cell lineage, includ-ing the closely related protein Ets2. In this report, we demonstrate that Ets1, but not Ets2, can block ASC formation despite the fact that Ets1 and Ets2 bind to apparently identical DNA sequence motifs and are thought to regulate overlapping sets of target genes. The DNA binding domain of Ets1 is required, but not sufficient by itself, to block ASC formation. In addition, less con-served regions within the N terminus of Ets1 play an important role in inhibiting B cell differentiation. Differences between the N termini of Ets1 and Ets2, rather than differences in the DNA binding domains, determine whether the proteins are capable of blocking ASC formation or not. Plasma cells or antibody-secreting cells (ASCs) are terminallydifferentiated B cell effectors that are specialized to secrete large amounts of immunoglobulin (Ig). The differentiation pro-cess of these cells involves expansion of the cytoplasmic compart-ment due to the substantial increase in the volume of the endo-plasmic reticulum, which is needed for increased Ig synthesis an