Autoantigenic germ cells exist outside the blood testis barrier

Area of Science:

• Immunology
• Reproductive Biology
• Cell Biology

Background:

• Preleptotene spermatocytes and spermatogonia are germ cells situated outside the Sertoli cell-mediated blood-testis barrier.
• These germ cells express autoantigens that are accessible to circulating antibodies.

Purpose of the Study:

• To investigate the accessibility of testis autoantigens to the immune system.
• To determine if autoantibodies can form immune complexes in testicular tissue.
• To assess the integrity of the blood-testis barrier as an immunological barrier.

Main Methods:

• Mice were immunized with syngeneic testis, with or without adjuvant.
• Immunoglobulin G (IgG) deposits were detected on testicular cells.
• Sera from orchiectomized and testes-intact mice were compared for antibody reactivity.
• IgG was eluted from positive testes and characterized.
• Reactivity of IgG deposits with specific antibody subclasses was analyzed.

Main Results:

• Detectable IgG deposits were found on cells at the periphery of seminiferous tubules in immunized mice.
• Sera from orchiectomized mice showed significantly higher reactivity with prepuberal testicular cells.
• Eluted IgG was specific for prepuberal testicular cells.
• IgG deposits were primarily of the IgG1 and IgG3 subclasses.
• IgG deposits were localized to specific stages (7-12) of the spermatogenic cycle, indicating stage-specific autoantigen expression.

Conclusions:

• Testis autoantigens are not completely sequestered and can be targeted by circulating autoantibodies.
• The formation of in situ immune complexes demonstrates that the blood-testis barrier is immunologically incomplete.
• Autoimmune responses against testicular components are possible and influenced by the stage of spermatogenesis.