Studies of congenitally immunologically mutant New Zealand mice: IX. Age-related microenvironmental effects on autoantibody production in NZB and NZB.X(id) mice studied by transplantation

K. R. Bray, M. Eric Gershwin, R. R. Skelly, A. Ahmed, P. W. Kincade

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The mechanism of polyclonal expansion of B cells and subsequent autoantibody production in New Zealand mice remains a critical question. We have been studying the requirements for autoantibody production both in NZB mice as well as NZB mice congenic with the X(id) gene of CBA/N mice. In this study, we have attempted to alter the immunologic phenotype of NZB.X(id) mice by transfer of cells from young and old NZB mice. There was little difficulty in restoring normal levels of serum IgM, IgG3, splenic Lyb-5 cells, and response to DNP-Ficoll in young NZB.X(id) mice that were injected with young NZB bone marrow cells. Although such animals had an almost immediate change in their immune profile to values characteristic of NZB mice, they required, much like unmanipulated NZB mice, a latency period of an additional 6 mo before autoantibodies were detected. In contrast, adult NZB.X(id) mice, who likewise developed an immune profile similar to NZB after transfer of bone marrow cells from young NZB mice, began to express autoantibodies immediately without any latency period. NZB.X(id) mice who were recipients of adult NZB bone marrow cells did not show sustained autoantibody production, reflecting the limited state of B cell precursors in adult NZB mice. Thus, the age of both donor cells and the age of recipient mice are critical factors for determining the latency period and the age at which autoantibodies will appear. Similarly we attempted to alter the production of autoantibodies in NZB mice that were irradiated and injected with bone marrow cells from NZB.X(id) animals. NZB mice had a major amelioration of disease when they received cell transfers from young NZB.X(id) mice. This amelioration, which included the acquisition of the immune profile of NZB.X(id) animals, was not seen in adult NZB mice that were recipients of young NZB cells. We suggest that although Lyb-5 cells may be the effective mechanism for autoantibody production, there are other interacting influences that may selectively turn on or turn off autoantibodies and that are required and are responsible for the latency period.

Original languageEnglish (US)
Pages (from-to)2913-2918
Number of pages6
JournalJournal of Immunology
Volume132
Issue number6
StatePublished - 1984

ASJC Scopus subject areas

  • Immunology

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