Abstract
BALB/c mice rendered chimeric at birth by injection of 10^8^ (A/J × BALB/c)F^1^ spleen cells develop a lupus‐like autoimmune disease linked to the activation of donor B cells by host T cells. As in vitro studies previously indicated that interleukin 4 (IL4) was a mediator of the interactions between T and B cells, we analyzed the intensity of Ia antigen expression on B cells of chimeric mice. Flow cytometric analysis with anti‐Ia monoclonal antibodies (mAb) revealed that B cells from spleens and lymph nodes of 2‐week‐old chimeric BALB/c mice displayed a two‐ to threefold increase in membrane Ia antigen expression, this increase still being present in spleens of 30‐week‐old animals. An increase in Ia antigen expression was also found in the small number of donor B cells detected in spleens and lymph nodes of chimeric mice. IL4 was the major stimulus leading to increased B cell Ia antigen expression, as this phenomenon was substantially prevented by in vivo treatment of chimeric mice with the anti‐IL4 11B11 mAb.
In vitro experiments revealed that host splenic T cells of chimeric mice, while unable to generate anti‐donor cytotoxic T lymphocytes, secreted significant amounts of IL4 when stimulated in mixed lymphocyte cultures (MLC) with donor alloantigens. This IL4 secretion led to an increased expression of Ia antigens on donor‐type F~1~ B cells present in MLC. No significant increase in Ia antigen expression was found on syngeneic BALB/c B cells co‐cultured with T cells from chimeric mice unless A/J B cells were added to the cultures.
Taken together, these findings indicate that increased Ia antigen expression on donor B cells is induced by IL4 secreted by anti‐donor Tcells. IL 4 released in this setting also leads to increased Ia antigen expression on host B cells through a bystander effect.