Transient depletion of B cells in young mice results in activation of regulatory T cells that inhibit development of autoimmune disease in adults.

Abstract

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.

• Authors: Shiguang Yu, Jason S Ellis, Robert Dunn, Marilyn R Kehry, Helen Braley-Mullen
• Journal: International immunology (Int Immunol) Vol. 24 Issue 4 Pg. 233-42 (Apr 2012) ISSN: 1460-2377 [Electronic] England
• PMID: 22298883 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD20

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage, immunology)
• Antigens, CD20 (immunology)
• B-Lymphocytes (immunology)
• Lymphocyte Depletion
• Mice
• Mice, Inbred NOD
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Thyroiditis, Autoimmune (immunology, pathology, prevention & control)