JAB1 is essential for B cell development and germinal center formation and inversely regulates fas ligand and Bcl6 expression

Selina Sitte, Joachim Gläsner, Julia Jellusova, Florian Weisel, Martina Panattoni, Ruggero Pardi, André Gessner

Research output: Contribution to journalArticlepeer-review

Abstract

Jun activation domain-binding protein 1 (JAB1) regulates ubiquitin-dependent protein degradation by deneddylation of cullin-based ubiquitin ligases and, therefore, plays a central role in regulating proliferation and apoptosis. Because these processes are decisive for B cell development, we investigated JAB1 functions in B cells by establishing a mouse strain with a B cell-specific JAB1 deletion.We show that JAB1 is essential for early B cell development, because the ablation of JAB1 expression blocks B cell development between the pro-B and pre-B cell stages. Furthermore, JAB1 deletion leads to aberrant expression of the apoptosis-triggering protein Fas ligand in pro-B cells. Concomitant B cell-specific overexpression of the antiapoptotic protein Bcl2 partially reverses the block in B cell development; rescued JAB1-deficient B cells reach the periphery and produce protective class-switched Abs after Borrelia burgdorferi infection. Interestingly, B cell-rescued mice exhibit no germinal centers but a striking extrafollicular plasma cell accumulation. In addition, JAB1 is essential for Bcl6 expression, a transcriptional repressor required for germinal center formation. These findings identify JAB1 as an important factor in checkpoint control during early B cell development, as well as in fate decisions in mature Ag-primed B cells.

Original languageEnglish
Pages (from-to)2677-2686
Number of pages10
JournalJournal of Immunology
Volume188
Issue number6
DOIs
Publication statusPublished - Mar 15 2012

ASJC Scopus subject areas

  • Immunology

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