| First Author | Meyer-Bahlburg A | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 7 | Pages | 4065-75 |
| PubMed ID | 19299704 | Mgi Jnum | J:147131 |
| Mgi Id | MGI:3839479 | Doi | 10.4049/jimmunol.0802961 |
| Citation | Meyer-Bahlburg A, et al. (2009) Reduced c-myc expression levels limit follicular mature B cell cycling in response to TLR signals. J Immunol 182(7):4065-75 |
| abstractText | The splenic B cell compartment is comprised of two major, functionally distinct, mature B cell subsets, i.e., follicular mature (FM) and marginal zone (MZ) B cells. Whereas MZ B cells exhibit a robust proliferative response following stimulation with the TLR4 ligand LPS, FM B cells display markedly delayed and reduced levels of proliferation to the identical stimulus. The current study was designed to identify a potential mechanism(s) accounting for this differential responsiveness. In contrast to the delay in cell cycle entry, FM and MZ B cells exhibited nearly identical LPS-driven alterations in the expression level of cell surface activation markers. Furthermore, both the NF-kappaB and mTOR signaling cascades were similarly activated by LPS stimulation in FM vs MZ B cells, while inducible activation of ERK and AKT were nearly absent in both subsets. MZ B cells, however, exhibited higher basal levels of phospho-AKT and pS6, consistent with a preactivated status. Importantly, both basal and LPS activation-induced c-myc expression was markedly reduced in FM vs MZ B cells and enforced c-myc expression fully restored the defective proliferative response in FM B cells. These data support a model wherein TLR responses in FM B cells are tightly regulated by limiting c-myc levels, thereby providing an important checkpoint to control nonspecific FM B cell activation in the absence of cognate Ag. |
