Influence of interleukin-2 deficiency on the generation of autoimmune B cells.
The production of auto-antibodies is one of the predominant characteristics of autoimmune disorders. Because IL-2 deficient mice develop autoimmunity, we asked how IL-2 deficiency might impair endogenous mechanisms of B cell tolerance. To this end, we mated BALB/c anti-dsDNA H chain knock-in mice, in which B cells producing anti-dsDNA antibodies are properly regulated, with IL-2 deficient mice and assessed the phenotype of their offspring. IL-2 deficient mice expressing the anti-dsDNA H chain knock-in allele developed anti-dsDNA antibodies of both IgM and IgG isotypes. Production of these antibodies occurred through the disruption of several mechanisms of endogenous tolerance, including deletion, maturational arrest, and follicular exclusion. In summary, our results suggest that IL-2 plays an important role in regulating B cell tolerance.
Wrenshall
Lucile E
LE
Division of Transplantation, University of Nebraska Medical Center, 983285 Nebraska Medical Center, Omaha, NE 68198-3285, USA.
Smith
Deandra R
DR
Stevens
Elliot T
ET
Miller
John D
JD
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000276:immunology; D017209:Apoptosis; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018925:Chemokines / Q000302:isolation & purification / Q000378:metabolism; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000974:Antibodies, Antinuclear; D018925:Chemokines; D007376:Interleukin-2
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