Thymic epithelial cell abnormalities in (NZB x H-2u)F1 mice

Area of Science:

• Immunology
• Genetics
• Autoimmune Diseases

Background:

• Thymic maturation requires thymocyte-stromal cell interaction.
• New Zealand black (NZB) mice exhibit thymic microenvironment defects.
• (NZB x NZW)F1 mice develop murine lupus and autoimmune manifestations.

Purpose of the Study:

• Investigate the genetic contribution of H-2 and non-H-2 loci to thymic abnormalities in lupus-prone mice.
• Examine thymic microenvironment alterations in (NZB x C57BL/10.PL)F1 and (NZB x PL/J)F1 mice.
• Correlate thymic defects with autoimmune disease development.

Main Methods:

• Utilized a panel of monoclonal antibodies to define the thymic microenvironment.
• Studied thymic architecture in NZB, NZW, (NZB x NZW)F1, (NZB x C57BL/10.PL)F1, (NZB x PL/J)F1, C57BL/6, and C57BL/10Sn mice.
• Assessed autoantibody titers (anti-DNA), proteinuria, and survival rates.

Main Results:

• NZW mice and controls showed normal thymic architecture.
• (NZB x NZW)F1 mice exhibited significantly altered thymic microenvironments.
• Mild thymic abnormalities were observed in (NZB x PL/J)F1 mice, but not in (NZB x C57BL/10.PL)F1 mice.
• (NZB x NZW)F1 mice developed lupus-like symptoms; (NZB x PL/J)F1 mice showed increased IgM anti-dsDNA antibodies without reduced survival.

Conclusions:

• Thymic stromal cell defects are directly associated with autoimmunity.
• The origin of these thymic defects is determined by non-H-2 genetic loci.
• Non-H-2 loci play a critical role in the development of thymic abnormalities and autoimmunity in lupus-prone mice.