BCLAF1 and responses to RAG-induced DNA breaks enforce pre-B cell checkpoint.

RAG-induced DNA double-strand break DDR in developing pre-B cells activates SPIC/BCLAF1, and loss of BCLAF1 disrupts pre-B cell checkpoint integrity during Igl recombination.

• Why it matters: Pre-B cells must coordinate pre-BCR signaling with DDR from RAG-generated DSBs to maintain a functional checkpoint during immunoglobulin light chain recombination.
• What they did: In vivo, pre-B cells transition between subpopulations dominated by pre-BCR or RAG DSB-induced DDR signals, and DDR programming during terminal pre-B stages involves SPIC/BCLAF1 activation.
• The result: BCLAF1 loss causes concomitant expression of pre-BCR and DDR programs with breakdown in segregation of clonal expansion and Igl recombination, preserving checkpoint integrity in vivo.