Immunoglobulin dysregulation in murine graft-vs-host disease: a hyper-IgE syndrome.
Immunoglobulin production, particularly IgE, is known to be dysregulated in graft-vs-host disease (GVHD). We examined serum levels of the highly T-dependent Ig isotypes, IgE, IgG1, and IgG2a, in two different mouse models of GVHD. GVHD across minor histocompatibility barriers is produced by injection of B10.D2 spleen cells into 600 rad irradiated BALB/c hosts. Both strains are H2d and mls b, but differ at the minor histocompatibility antigens. As GVHD progresses there is a rapid rise in serum IgE (300-fold) and IgG1 (2.5-fold) with a peak at Day 14. Concomitantly, IgG2a falls. Serum immunoglobulin levels return to normal by 11 weeks. The rise in IgE is abolished by increased (900 rad) recipient irradiation, suggesting that host-derived factors are important. GVHD across major histocompatibility barriers is produced by injection of DBA/2 spleen cells into unirradiated or 600 rad irradiated (B6 x DBA/2)F1 hosts. Only in the irradiated recipients is there severe Ig dysregulation. In this situation there is a 100-fold rise in IgE, and 5- to 10-fold rises in IgG1 and IgG2a. While the results in GVHD across minor barriers suggest stimulation of T helper cells secreting IL-4, the increase in IgE, IgG1, and IgG2a levels in GVHD across major barriers suggests activation of IL-4 and IFN-gamma-secreting T cells. These results indicate that different mechanisms may be operating in these two models of GVH. Murine GVHD can serve as a model for studying dysgammaglobulinemias in general and for hyper-IgE formation in particular.
Claman
H N
HN
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Spiegelberg
H L
HL
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D015778:Minor Histocompatibility Antigens / Q000276:immunology
D006649:Histocompatibility Antigens; D007074:Immunoglobulin G; D015778:Minor Histocompatibility Antigens; D007073:Immunoglobulin E