BCL6 is critical for the development of a diverse primary B cell repertoire

Duy, Cihangir; Yu, Jingwei; Nahar, Rahul; Swaminathan, Srividya; Kweon, Soo Mi; Polo, José M.; Valls, Ester; Klemm, Lars; Shojaee, Seyedmehdi; Cerchietti, Leandro; Schuh, Wolfgang; Jäck, Hans‐Martin; Hurtz, Christian; Ramezani-Rad, Parham; Herzog, Sebastian; Jumaa, Hassan; Koeffler, H. Phillip; Alborán, Ignacio Moreno de; Melnick, Ari; Ye, B. Hilda; Müschen, Markus

doi:10.1084/jem.20091299

Cited by 114 publications

(98 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, we do not exclude the possibility that the ZIP10-Zn signaling axis simultaneously modulates the related signaling pathways. A Zn finger transcriptional factor BCL6 is critical for cell survival at the pre-B-cell transitional stage (41). In addition, E2A is also essential for B-cell development, and its absence results in growth arrest (42) and caspase-dependent apoptosis (43).…”

Section: Discussionmentioning

confidence: 99%

Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development

Miyai

Hojyo

Ikawa³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

111

View full text Add to dashboard Cite

The immune system is influenced by the vital zinc (Zn) status, and Zn deficiency triggers lymphopenia; however, the mechanisms underlying Zn-mediated lymphocyte maintenance remain elusive. Here we investigated ZIP10, a Zn transporter expressed in the early B-cell developmental process. Genetic ablation of Zip10 in early B-cell stages resulted in significant reductions in B-cell populations, and the inducible deletion of Zip10 in pro-B cells increased the caspase activity in parallel with a decrease in intracellular Zn levels. Similarly, the depletion of intracellular Zn by a chemical chelator resulted in spontaneous caspase activation leading to cell death. Collectively, these findings indicated that ZIP10-mediated Zn homeostasis is essential for early B-cell survival. Moreover, we found that ZIP10 expression was regulated by JAK-STAT pathways, and its expression was correlated with STAT activation in human B-cell lymphoma, indicating that the JAK-STAT-ZIP10-Zn signaling axis influences the B-cell homeostasis. Our results establish a role of ZIP10 in cell survival during early B-cell development, and underscore the importance of Zn homeostasis in immune system maintenance.B-lymphocyte | apoptosis | cytokine | bone marrow | zinc-signaling axis

show abstract

Section: Discussionmentioning

confidence: 99%

Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development

Miyai

Hojyo

Ikawa³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

111

View full text Add to dashboard Cite

show abstract

“…It remains to be investigated whether JAB1 enhances Bcl6 translation and/or protein stability. A recent study showed a critical role for Bcl6 in early B cell development (44). We speculate that the observed B cell development block might be partially caused by a putative absence of Bcl6 in JAB1-deficient early B cells.…”

Section: Discussionmentioning

confidence: 62%

JAB1 Is Essential for B Cell Development and Germinal Center Formation and Inversely Regulates Fas Ligand and Bcl6 Expression

Sitte

Gläsner

Jellusova

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

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.

show abstract

“…formation of a normal, diverse polyclonal repertoire (Duy et al, 2010). Bcl-6 can also facilitate osteoblastogenesis by recuperating the Runx2 nuclear translocation inhibited by STAT1 and can suppress osteoclastogenesis by attenuating NFATc1 target gene transcription (Fujie et al, 2015;Miyauchi et al, 2010).…”

Section: Reciprocal Interaction Between Immune System and Skeletal Symentioning

confidence: 99%

“…Bcl-6 can also facilitate osteoblastogenesis by recuperating the Runx2 nuclear translocation inhibited by STAT1 and can suppress osteoclastogenesis by attenuating NFATc1 target gene transcription (Fujie et al, 2015;Miyauchi et al, 2010). Bcl-6 / mice exhibit a distinct OP phenotype, with a markedly reduced new immature B cell pool in the bone marrow and impaired clonal diversity (Duy et al, 2010;Miyauchi et al, 2010 (Despars et al, 2013;Hamerman et al, 2005).…”

Section: Reciprocal Interaction Between Immune System and Skeletal Symentioning

confidence: 99%

Osteoimmunology: memorandum for rheumatologists

Huang

Zhang

2016

Sci. China Life Sci.

View full text Add to dashboard Cite

Rapid progress has been made in exploring the connections between the skeletal system and the immune system over the past decade. Bone tissue forms developmental niches for hematopoietic stem cells, and activated immune cells are involved in bone metabolism regulation and are potent mediators of osteoporosis and bone erosion under pathological conditions. The interdisciplinary field of osteoimmunology has emerged to pool the knowledge of the interdependence of these two systems, including the shared ligands and receptors, their crosstalk and interaction, and common intracellular signaling pathways with bidirectional influence. The receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) triad is the key vinculum, with multifaceted potency, being not only essential for osteoclastogenesis but also critical for lymph node organogenesis and lymphopoiesis as well as for immune regulation. In this review, we summarize the progress in this area, focusing on those aspects of interest concerning rheumatic diseases. osteoimmunology, bone remodeling, osteoclastogenesis, immune cells, RANKLCitation:

show abstract

BCL6 is critical for the development of a diverse primary B cell repertoire

Cited by 114 publications

References 46 publications

Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development

Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development

JAB1 Is Essential for B Cell Development and Germinal Center Formation and Inversely Regulates Fas Ligand and Bcl6 Expression

Osteoimmunology: memorandum for rheumatologists

Contact Info

Product

Resources

About