First Author | Mandik-Nayak L | Year | 2000 |
Journal | J Immunol | Volume | 164 |
Issue | 3 | Pages | 1161-8 |
PubMed ID | 10640726 | Mgi Jnum | J:59958 |
Mgi Id | MGI:1352340 | Doi | 10.4049/jimmunol.164.3.1161 |
Citation | Mandik-Nayak L, et al. (2000) Functional consequences of the developmental arrest and follicular exclusion of anti-double-stranded DNA B cells. J Immunol 164(3):1161-8 |
abstractText | Anti-dsDNA B cells are actively tolerized in nonautoimmune BALB/c mice, as manifested by their developmental arrest, follicular exclusion, and rapid turnover rate. Previously, we have documented changes in the maturation status and follicular localization of anti-dsDNA B cells in autoimmune-prone MRL (+/+ and lpr/lpr) mice. To determine whether these differences in developmental status and follicular localization affect the functional capacity of anti-dsDNA B cells, we have now compared their in vivo life spans and their responses to in vitro stimuli. Our study shows that although anti-dsDNA B cells from both BALB/c and MRL-+/+ mice are localized to the T/B interface, only those in BALB/c mice have a rapid turnover rate. Therefore, the immature status and not the exclusion from the B cell follicle correlates with a shortened life span. Interestingly, apoptotic anti-dsDNA B cells were not detected at the T/B interface in BALB/c mice, suggesting that they are not dying there. This study also demonstrates that anti-dsDNA B cells, regardless of maturation status or follicular localization, are able to proliferate and up-regulate the costimulatory molecule B7-2 in response to CD40 ligand and IL-4. Therefore, one of the critical in vivo differences between anti-dsDNA B cells in BALB/c and MRL-+/+ mice compared with MRL-lpr/lpr mice may be the availability of T cell help. |