| First Author | Yu M | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 11 | Pages | 5185-93 |
| PubMed ID | 23087406 | Mgi Jnum | J:190683 |
| Mgi Id | MGI:5449467 | Doi | 10.4049/jimmunol.1102952 |
| Citation | Yu M, et al. (2012) Critical role of B cell lymphoma 10 in BAFF-regulated NF-kappaB activation and survival of anergic B cells. J Immunol 189(11):5185-93 |
| abstractText | Anergy is a key physiological mechanism for restraining self-reactive B cells. A marked portion of peripheral B cells are anergic B cells that largely depend on BAFF for survival. BAFF activates the canonical and noncanonical NF-kappaB pathways, both of which are required for B cell survival. In this study we report that deficiency of the adaptor protein B cell lymphoma 10 (Bcl10) impaired the ability of BAFF to support B cell survival in vitro, and it specifically increased apoptosis in anergic B cells in vivo, dramatically reducing anergic B cells in mice. Bcl10-dependent survival of self-reactive anergic B cells was confirmed in the Ig hen egg lysozyme/soluble hen egg lysozyme double-transgenic mouse model of B cell anergy. Furthermore, we found that BAFF stimulation induced Bcl10 association with IkappaB kinase beta, a key component of the canonical NF-kappaB pathway. Consistently, Bcl10-deficient B cells were impaired in BAFF-induced IkappaBalpha phosphorylation and formation of nuclear p50/c-Rel complexes. Bcl10-deficient B cells also displayed reduced expression of NF-kappaB2/p100, severely reducing BAFF-induced nuclear accumulation of noncanonical p52/RelB complexes. Consequently, Bcl10-deficient B cells failed to express Bcl-x(L), a BAFF-induced NF-kappaB target gene. Taken together, these data demonstrate that Bcl10 controls BAFF-induced canonical NF-kappaB activation directly and noncanonical NF-kappaB activation indirectly. The BAFF-R/Bcl10/NF-kappaB signaling axis plays a critical role in peripheral B cell tolerance by regulating the survival of self-reactive anergic B cells. |
