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Anti–DNA B Cells in MRL/lpr Mice Show Altered Differentiation and Editing Pattern
We have studied the regulation of anti–DNA B cells in transgenic mice with a heavy chain transgene (3H9H/56R). This transgene codes for a heavy chain that forms anti–double-stranded DNA (dsDNA) antibody when paired with most members of the endogenous Vκ repertoire, but certain L chains, referred to...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2002
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196070/ https://www.ncbi.nlm.nih.gov/pubmed/12486097 http://dx.doi.org/10.1084/jem.20021560 |
Sumario: | We have studied the regulation of anti–DNA B cells in transgenic mice with a heavy chain transgene (3H9H/56R). This transgene codes for a heavy chain that forms anti–double-stranded DNA (dsDNA) antibody when paired with most members of the endogenous Vκ repertoire, but certain L chains, referred to as Vκ editors, do not sustain dsDNA binding in combination with 3H9H/56R. In the nonautoimmune 3H9H/56R BALB/c, most B cells generated do not bind DNA because the transgene itself is edited or is associated with a Vκ editor. A minor population of B cells (30%) bind dsDNA and express the λ1 light chain (known to sustain 3H9H/56R DNA binding). These 3H9/56R/λ1 B cells coexpress a κ editor, and we propose that the down-regulation of the anti-DNA BCR caused by the dual L chain expression may prevent activation of this κ/λ population. These κ/λ B cells are sequestered in the marginal zone. Here, we studied the influence of autoimmunity on expression and regulation of 3H9H/56R. In 3H9H/56R MRL/lpr mice, the expression of anti-dsDNA is vastly accelerated. Anti–dsDNA B cells use noneditor κs but, in addition, most anti–dsDNA B cells have edited the heavy chain transgene. λ1 B cells (without the coexpression of a κ editor) are found and the κ/λ1 MZ population is absent. Our results suggest that improper editing and failure to sequester autoreactive B cells may contribute to the breakdown of tolerance in MRL/lpr mice. |
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