Increased expression of Ia antigens on B cells after neonatal induction of lymphoid chimerism in mice: role of interleukin 4.
BALB/c mice rendered chimeric at birth by injection of 10(8) (A/J X BALB/c)F1 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 IL 4 when stimulated in mixed lymphocyte cultures (MLC) with donor alloantigens. This IL4 secretion led to an increased expression of Ia antigens on donor-type F1 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 T cells. IL4 released in this setting also leads to increased Ia antigen expression on host B cells through a bystander effect.
Abramowicz
D
D
Laboratoire Pluridisciplinaire de Recherche Expérimentale Biomédicale, Cliniques Universitaires de Bruxelles, Belgium.
Doutrelepont
J M
JM
Lambert
P
P
Van der Vorst
P
P
Bruyns
C
C
Goldman
M
M
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002678:Chimera / Q000276:immunology*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000502:physiology*; D008198:Lymph Nodes / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D015847:Interleukin-4