Protective and pathogenic roles for B cells during systemic autoimmunity in NZB/W F1 mice.

Abstract

Delineating the relative contributions of B lymphocytes during the course of autoimmune disease has been difficult. Therefore, the effects of depleting all mature B cells using a potent CD20 mAb, or of depleting circulating and marginal zone B cells using a ligand-blocking CD22 mAb, were compared in NZB/W F(1) mice, a model for human systemic lupus erythematosus. Single low-dose mAb treatments depleted B cells efficiently in both NZB/W F(1) and C57BL/6 mice. Prophylactic B cell depletion by repeated CD20 mAb treatments prolonged survival during pristane-accelerated lupus in NZB/W F(1) mice, whereas CD22 mAb had little effect. Despite effective B cell depletion, neither mAb treatment prevented autoantibody generation. In addition, CD20, CD22, and control mAb-treated NZB/W F(1) mice developed anti-mouse IgG autoantibodies in contrast to parental NZB and NZW strains, which may have reduced the effectiveness of B cell depletion. Despite this, low-dose CD20 mAb treatment initiated in 12-28-wk-old mice, and administered every 4 wk thereafter, significantly delayed spontaneous disease in NZB/W F(1) mice. By contrast, B cell depletion initiated in 4-wk-old mice hastened disease onset, which paralleled depletion of the IL-10-producing regulatory B cell subset called B10 cells. B10 cells were phenotypically similar in NZB/W F(1) and C57BL/6 mice, but were expanded significantly in young NZB/W F(1) mice. Thus, B cell depletion had significant effects on NZB/W F(1) mouse survival that were dependent on the timing of treatment initiation. Therefore, distinct B cell populations can have opposing protective and pathogenic roles during lupus progression.

• Authors: Karen M Haas, Rei Watanabe, Takashi Matsushita, Hiroko Nakashima, Nobuko Ishiura, Hitoshi Okochi, Manabu Fujimoto, Thomas F Tedder
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 184 Issue 9 Pg. 4789-800 (May 01 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20368280 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD20
• Autoantibodies
• Cd22 protein, mouse
• Sialic Acid Binding Ig-like Lectin 2
• Terpenes
• pristane

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage, therapeutic use)
• Antigens, CD20 (immunology)
• Autoantibodies (biosynthesis)
• B-Lymphocyte Subsets (immunology, pathology)
• Crosses, Genetic
• Disease Models, Animal
• Female
• Lupus Erythematosus, Systemic (immunology, mortality, pathology)
• Lupus Nephritis (immunology, mortality, pathology)
• Lymphocyte Count
• Lymphocyte Depletion
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred NZB
• Sialic Acid Binding Ig-like Lectin 2 (immunology)
• Survival Rate
• Terpenes (toxicity)