MHC control of IL-4-dependent enhancement of B cell Ia expression and Ig class switching in mice treated with mercuric chloride.
Systemic treatment of susceptible mouse strains with HgCl2 is known to induce elevated serum concentrations of IgG1, IgG2A, and IgE, formation of antinuclear (ANA) and antinucleolar autoantibodies (ANolA), and immune glomerulonephritis. The development of these HgCl2-induced immunological alterations requires CD4+ T cells. The H-2s haplotype encodes susceptibility and, as far as studied, H-2d determines resistance. For a better understanding of susceptibility and resistance to HgCl2 at the level of Th and B cells, we compared the effects of HgCl2 treatment in the H-2 congenic mouse strains B10.S (H-2s) and B10.D2/n (H-2d). We show that (1) H-2s but not H-2d mice responded to HgCl2 treatment with massive activation of their B cells and switch to IgE, IgG1, and IgG2A; (2) both H-2s and H-2d mice responded to HgCl2 with IL-4-dependent increases in B cell Ia expression, but significantly higher levels were induced in H-2s than in H-2d mice; (3) splenic CD4+ T cells of HgCl2-treated H-2s mice showed a strong increase in IL-4 mRNA, whereas those of H-2d mice showed only a weak increase; (4) both H-2s and H-2d mice expressed enhanced splenic numbers of CD45RBlo CD4+ T cells, suggesting activation of T cells in both strains. These results indicate that the MHC, presumably by its class II loci, modulates the T cell response to the etiologic agent HgCl2, and, hence, determines which type of immune effector mechanism is activated. A possible explanation of the observed strain difference is that H-2s and H-2d mice responded to systemic treatment with HgCl2 by preferential activation of Th2 and Th1 cells, respectively.
van Vliet
E
E
Division of Immunology, Heinrich Heine University of Düsseldorf, FRG.
Uhrberg
M
M
Stein
C
C
Gleichmann
E
E
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000502:physiology*; D007132:Immunoglobulin Isotypes / Q000032:analysis; D015847:Interleukin-4 / Q000235:genetics / Q000494:pharmacology*; D007700:Kinetics; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000502:physiology*; D008627:Mercuric Chloride / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000032:analysis
D000949:Histocompatibility Antigens Class II; D007132:Immunoglobulin Isotypes; D012333:RNA, Messenger; D015847:Interleukin-4; D008627:Mercuric Chloride; D017493:Leukocyte Common Antigens