| First Author | Duy C | Year | 2010 |
| Journal | J Exp Med | Volume | 207 |
| Issue | 6 | Pages | 1209-21 |
| PubMed ID | 20498019 | Mgi Jnum | J:163422 |
| Mgi Id | MGI:4821918 | Doi | 10.1084/jem.20091299 |
| Citation | Duy C, et al. (2010) BCL6 is critical for the development of a diverse primary B cell repertoire. J Exp Med 207(6):1209-21 |
| abstractText | BCL6 protects germinal center (GC) B cells against DNA damage-induced apoptosis during somatic hypermutation and class-switch recombination. Although expression of BCL6 was not found in early IL-7-dependent B cell precursors, we report that IL-7Ralpha-Stat5 signaling negatively regulates BCL6. Upon productive VH-DJH gene rearrangement and expression of a mu heavy chain, however, activation of pre-B cell receptor signaling strongly induces BCL6 expression, whereas IL-7Ralpha-Stat5 signaling is attenuated. At the transition from IL-7-dependent to -independent stages of B cell development, BCL6 is activated, reaches expression levels resembling those in GC B cells, and protects pre-B cells from DNA damage-induced apoptosis during immunoglobulin (Ig) light chain gene recombination. In the absence of BCL6, DNA breaks during Ig light chain gene rearrangement lead to excessive up-regulation of Arf and p53. As a consequence, the pool of new bone marrow immature B cells is markedly reduced in size and clonal diversity. We conclude that negative regulation of Arf by BCL6 is required for pre-B cell self-renewal and the formation of a diverse polyclonal B cell repertoire. |
