Functional role in self reactivity for Ia antigens on murine synovial cells

Cultures of synovial cells from normal CBA mice were established after collagenase treatment of synovial tissue collected from the knee joint. Morphological studies using light and electron microscopy have shown that confluent monolayers are composed of 90% triangular or stellate dendritic cells with numerous microvilli and 5% secreting cells containing many dense granules. Less than 5% contaminating cells, such as fibroblasts or macrophages, are present. The class I and class II antigens of the major histocompatibility complex, detected by indirect immunofluorescence or complement-dependent cytotoxicity, are expressed on the cell surface of normal CBA synovial monolayers. Functional Ia antigens borne by synoviocytes are evidenced by the proliferative responses they elicit from syngeneic (or allogeneic) spleen cells after a 3-day co-culture. Similarly, monolayers of Ia+ synovial cells were obtained from both MRL/lpr mice, which spontaneously develop an autoimmune syndrome, and the control MRL/n mice. Spleen cells from young MRL/lpr exhibited significantly higher levels of blastogenesis in syngeneic co-cultures than those from MRL/n mice. Conversely, with advancing age the syngeneic proliferative responses declined minimally for MRL/lpr mice and were unchanged for MRL/n mice. These findings suggest that Ia+ synovial cells can effectively interact with syngeneic lymphocytes and may initiate autoimmune reactivity.