Mouse epidermal Ia molecules have a bone marrow origin

Abstract

The major histocompatibility or H–2 complex of the mouse is divided into five regions (K, I, S, G and D)¹. Genes in the I region regulate immune responses². The I region has several subregions which are designated I–A, I–B, I–J, I–E and I–C. The I–A and I–E subregions also code for a set of serologically detected cell-surface alloantigens, designated Ia antigens³. The relationship between the genes regulating the immune response and those encoding the serologically detectable alloantigens is still unknown. A number of species including man, rats and guinea pigs contain genetic regions apparently equivalent to the murine I region. Ia molecules are integral cell-surface glycoproteins that consist of two subunits of approximate molecular weights 35,000 (α) and 28,000 (β). Unlike the classical transplantation antigens which are present on almost all cells, the Ia antigens are found primarily on cells of the immune system—lymphocytes and macrophages^4–6. A notable exception has been the demonstration of Ia antigens in mice, or Ia-like antigens in other mammals, on epidermal cells^6–13. There is controversy about the numbers of Ia-positive cells in the epidermis. Fluorescence studies in humans^11,12, guinea pigs¹⁴ and mice¹⁵ indicate that only about 5% of epidermal cells are Ia positive. These cells were identified by morphological criteria as the macrophage-like Langerhans cells. However, cytotoxicity studies in mice using anti-Ia sera indicate that a majority of epidermal cells (up to 90%) are Ia positive^6–8. The reason for this discrepancy is not known. Here we demonstrate that the epidermal Ia molecules are synthesised by bone marrow-derived cells, presumably Langerhans cells.