Expression of an anti-DNA-associated VH gene in immunized and autoimmune mice
| Autor: | A Ash-Lerner, M Ginsberg-Strauss, Y Pewzner-Jung, D D Desai, T N Marion, D Eilat |
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| Rok vydání: | 1997 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 159:1508-1519 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.159.3.1508 |
| Popis: | The J558 family BW-16 VH gene is closely associated with the autoimmune response to DNA of lupus-prone mice. We have followed the expression of VHBW-16-encoded heavy chains in cDNA libraries prepared from unmanipulated normal (C3H, AKR) and autoimmune (New Zealand Black/New Zealand White F1) mice, and from mice immunized with a highly immunogenic peptide/DNA complex. The prevalence, clonal heterogeneity, and structural properties (somatic mutation, complementarity-determining region 3 composition) of these H chains were investigated, and the DNA affinity of VHBW-16-encoded hybridoma mAb was measured in solution. We find that H chains encoded by VHBW-16 are very rare in Igs of normal mice, but increase significantly in peptide/DNA-immunized mice, and dramatically in diseased mice. The experimentally induced VHBW-16-encoded H chains are clonally restricted, somatically mutated, partly switched from IgM to IgG, and give rise to anti-DNA Abs with low affinity. In contrast, the VHBW-16-encoded H chains from diseased New Zealand Black/New Zealand White mice are clonally heterogeneous, exclusively of the IgG isotype, and produce high affinity anti-DNA autoantibodies. We conclude that the experimentally induced and spontaneous immune responses to DNA are qualitatively similar, but quantitatively different, and may truly reflect the principles of self immunologic tolerance. |
| Databáze: | OpenAIRE |
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