Transient depletion of B cells in young mice results in activation of regulatory T cells that inhibit development of autoimmune disease in adults.
B-cell depletion therapy can be effective for treating B-cell lymphomas as well as many human and murine autoimmune diseases. B-cell-deficient mice are normally resistant to spontaneous autoimmune thyroiditis (SAT), but they develop SAT if regulatory T cells are transiently depleted during the first 3-6 weeks after birth. This was also a critical time when B-cell depletion effectively inhibited development of SAT in adult mice. The current study was undertaken to test the hypothesis that transient depletion of B cells using anti-CD20 would be sufficient to suppress SAT if B cells were depleted early in life and that inhibition of SAT would be due to the activity of Treg that functioned most effectively when B cells were absent or low. The results presented here support this hypothesis and indicate that development of autoimmune disease in adults is effectively inhibited when anti-CD20 is administered 1-3 weeks after birth. After 3 weeks, transient B-cell depletion is no longer effective, and B-cell depletion must be maintained to effectively suppress autoimmune disease. B-cell depletion in 1- to 3-week-old mice depletes all B-cell subsets, whereas B-cell depletion initiated in adults spares many marginal zone B cells. Following early B-cell depletion, splenic Treg increase in number, and depletion of Treg reverses the inhibitory effect of anti-CD20 on disease development. Early transient depletion of B cells could be useful for preventing autoimmune disease in individuals at high risk for developing autoimmune diseases as adults.
Department of Medicine, University of Missouri, Columbia, MO 65212, USA.
Shiguang
S
Yu
Jason S
JS
Ellis
Robert
R
Dunn
Marilyn R
MR
Kehry
Helen
H
Braley-Mullen
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D016688:Mice, Inbred NOD; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20