| First Author | Aaron T | Year | 2023 |
| Journal | J Immunol | Volume | 210 |
| Issue | 5 | Pages | 595-608 |
| PubMed ID | 36645344 | Mgi Jnum | J:340988 |
| Mgi Id | MGI:7471303 | Doi | 10.4049/jimmunol.2200053 |
| Citation | Aaron T, et al. (2023) TNF-alpha Limits Serological Memory by Disrupting the Bone Marrow Niche. J Immunol 210(5):595-608 |
| abstractText | Both infection and autoimmune disease can disrupt pre-existing Ab titers leading to diminished serological memory, yet the underlying mechanisms are not well understood. In this article, we report that TNF-alpha, an inflammatory cytokine, is a master regulator of the plasma cell (PC) niche in the bone marrow (BM). Acute rTNF-alpha treatment depletes previously existing Ab titers after vaccination by limiting PC occupancy or retention in the BM. Consistent with this phenomenon, mice lacking TNF-alpha signaling have elevated PC capacity in the BM and higher Ab titers. Using BM chimeric mice, we found that PC egress from the BM is regulated in a cell-extrinsic manner, by radiation-resistant cells via TNF-alpha receptor 1 signaling, leading to increased vascular permeability and CD138 downregulation on PCs. PC motility and egress in the BM are triggered within 6 h of recombinant TNF-alpha treatment. In addition to promoting egress, TNF-alpha signaling also prevented re-engraftment into the BM, leading to reduced PC survival. Although other inflammatory stimuli can promote PC egress, TNF-alpha signaling is necessary for limiting the PC capacity in the BM. Collectively, these data characterize how TNF-alpha-mediated inflammation attenuates the durability of serological memory and shapes the overall size and composition of the Ab-secreting cell pool in the BM. |
