Functional consequences of the developmental arrest and follicular exclusion of anti-double-stranded DNA B cells.
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.
Mandik-Nayak
L
L
The Wistar Institute, Philadelphia, PA 19104, USA.
Seo
S j
Sj
Eaton-Bassiri
A
A
Allman
D
D
Hardy
R R
RR
Erikson
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000235:genetics; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D018448:Models, Immunological; D008969:Molecular Sequence Data; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000974:Antibodies, Antinuclear; D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains; D008562:Membrane Glycoproteins; D004247:DNA