Protective and pathogenic roles for B cells during systemic autoimmunity in NZB/W F1 mice.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Haas, KM; Watanabe, R; Matsushita, T; Nakashima, H; Ishiura, N; Okochi, H; Fujimoto, M; Tedder, TF
Published Date
- May 1, 2010
Published In
Volume / Issue
- 184 / 9
Start / End Page
- 4789 - 4800
PubMed ID
- 20368280
Pubmed Central ID
- PMC3734557
Electronic International Standard Serial Number (EISSN)
- 1550-6606
Digital Object Identifier (DOI)
- 10.4049/jimmunol.0902391
Language
- eng
Conference Location
- United States