| First Author | Chaimowitz NS | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 8 | Pages | e42694 |
| PubMed ID | 22880085 | Mgi Jnum | J:189822 |
| Mgi Id | MGI:5447096 | Doi | 10.1371/journal.pone.0042694 |
| Citation | Chaimowitz NS, et al. (2012) ADAM10 regulates transcription factor expression required for plasma cell function. PLoS One 7(8):e42694 |
| abstractText | A disintegrin and metalloprotease 10 (ADAM10) is a key regulator of cellular processes by shedding extracellular domains of transmembrane proteins. We have previously demonstrated that deletion of B cell expressed ADAM10 results in changes in lymphoid tissue architecture and impaired germinal center (GC) formation. In this study, mice were generated in which ADAM10 is deleted in B cells following class switch recombination (ADAM10(Delta/Delta)IgG1-cre(+/-) mice). Despite normal GC formation, antibody responses were impaired in ADAM10(Delta/Delta)IgG1-cre(+/-) mice, implicating ADAM10 in post-GC and extrafollicular B cell terminal differentiation. Surprisingly, plasma cell (PC) numbers were normal in ADAM10(Delta/Delta)IgG1-cre(+/-) mice when compared to controls. However, PCs isolated from ADAM10(Delta/Delta)IgG1-cre(+/-) mice exhibited decreased expression of transcription factors important for PC function: Prdm1, Xbp1 and Irf4. Bcl6 is a GC transcriptional repressor that inhibits the PC transcriptional program and thus must be downregulated for PC differentiation to occur. Bcl6 expression was increased in PCs isolated from ADAM10(Delta/Delta)IgG1-cre(+/-) mice at both the mRNA and protein level. These results demonstrate that ADAM10 is required for proper transcription factor expression in PCs and thus, for normal PC function. |
