| First Author | Xu LS | Year | 2023 |
| Journal | J Immunol | Volume | 211 |
| Issue | 1 | Pages | 71-80 |
| PubMed ID | 37195219 | Mgi Jnum | J:340103 |
| Mgi Id | MGI:7518463 | Doi | 10.4049/jimmunol.2300122 |
| Citation | Xu LS, et al. (2023) Spi-C and PU.1 Counterregulate Rag1 and Igkappa Transcription to Effect Vkappa-Jkappa Recombination in Small Pre-B Cells. J Immunol 211(1):71-80 |
| abstractText | B cell development requires the ordered rearrangement of Ig genes encoding H and L chain proteins that assemble into BCRs or Abs capable of recognizing specific Ags. Igkappa rearrangement is promoted by chromatin accessibility and by relative abundance of RAG1/2 proteins. Expression of the E26 transformation-specific transcription factor Spi-C is activated in response to dsDNA double-stranded breaks in small pre-B cells to negatively regulate pre-BCR signaling and Igkappa rearrangement. However, it is not clear if Spi-C regulates Igkappa rearrangement through transcription or by controlling RAG expression. In this study, we investigated the mechanism of Spi-C negative regulation of Igkappa L chain rearrangement. Using an inducible expression system in a pre-B cell line, we found that Spi-C negatively regulated Igkappa rearrangement, Igkappa transcript levels, and Rag1 transcript levels. We found that Igkappa and Rag1 transcript levels were increased in small pre-B cells from Spic-/- mice. In contrast, Igkappa and Rag1 transcript levels were activated by PU.1 and were decreased in small pre-B cells from PU.1-deficient mice. Using chromatin immunoprecipitation analysis, we identified an interaction site for PU.1 and Spi-C located in the Rag1 promoter region. These results suggest that Spi-C and PU.1 counterregulate Igkappa transcription and Rag1 transcription to effect Igkappa recombination in small pre-B cells. |
