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Autoreactive B Cells in Lupus-Prone New Zealand Black Mice Exhibit Aberrant Survival and Proliferation in the Presence of Self-Antigen In Vivo¹

Nan-Hua Chang^*, Ralph MacLeod^* and Joan E. Wither^2,*,,

^* Arthritis Centre of Excellence, Toronto Western Research Institute, Toronto, Ontario, Canada; Department of Immunology, University of Toronto, Toronto, Ontario, Canada; and Department of Medicine, University Health Network, Toronto, Ontario, Canada

To identify defects in B cell tolerance that may contribute to the production of autoantibodies in New Zealand Black (NZB) mice, we crossed soluble hen egg white lysozyme (sHEL) and anti-HEL Ig transgenes (Ig Tg) onto the NZB background. In this study, we have examined one of the first checkpoints involved in maintenance of peripheral B cell tolerance, follicular exclusion and elimination of self-reactive B cells in the absence of T cell help. Freshly isolated anti-HEL Ig Tg B cells were labeled with CFSE, adoptively transferred into sHEL recipients, and the fate of self-reactive anti-HEL Ig Tg B cells was followed using flow cytometry and immunofluorescence microscopy. Although anti-HEL Ig Tg B cells from NZB mice are appropriately excluded from B cell follicles in NZB sHEL recipient mice, they demonstrate aberrant survival, proliferation, and generation of anti-HEL Ab-producing cells. This abnormal response results from an intrinsic defect in NZB B cells, requires the presence of CD4⁺ T cells, and is facilitated by the splenic environment in NZB mice. Thus, NZB mice have immune defects that interact synergistically to allow autoreactive B cells to become activated despite the presence of tolerizing autoantigens.

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The JI 2004 172: 1331-1332. [Full Text]  

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