| First Author | Yan H | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 5 | Pages | 1146-1157 |
| PubMed ID | 31932498 | Mgi Jnum | J:285615 |
| Mgi Id | MGI:6392183 | Doi | 10.4049/jimmunol.1901170 |
| Citation | Yan H, et al. (2020) B Cell Endosomal RAB7 Promotes TRAF6 K63 Polyubiquitination and NF-kappaB Activation for Antibody Class-Switching. J Immunol 204(5):1146-1157 |
| abstractText | Upon activation by CD40 or TLR signaling, B lymphocytes activate NF-kappaB to induce activation-induced cytidine deaminase and, therefore, Ig class switch DNA recombination, as central to the maturation of the Ab and autoantibody responses. In this study, we show that NF-kappaB activation is boosted by colocalization of engaged immune receptors, such as CD40, with RAB7 small GTPase on mature endosomes, in addition to signals emanating from the receptors localized on the plasma membrane, in mouse B cells. In mature endosomes, RAB7 directly interacts with TRAF6 E3 ubiquitin ligase, which catalyzes K63 polyubiquitination for NF-kappaB activation. RAB7 overexpression in Cd19(+/cre)Rosa26(fl-STOP-fl-Rab7) mouse B cells upregulates K63 polyubiquitination activity of TRAF6, enhances NF-kappaB activation and activation-induced cytidine deaminase induction, and boosts IgG Ab and autoantibody levels. This, together with the extensive intracellular localization of CD40 and the strong correlation of RAB7 expression with NF-kappaB activation in mouse lupus B cells, shows that RAB7 is an integral component of the B cell NF-kappaB activation machinery, likely through interaction with TRAF6 for the assembly of "intracellular membrane signalosomes." |
