Regulation by interferon alpha of immunoglobulin isotype selection and lymphokine production in mice.
Antigens and infectious agents that stimulate interferon alpha(IFN-alpha) production in mice induce antibody responses that are predominantly of the immunoglobulin (Ig)G2a isotype and contain little or no IgE. This suggested the possibility that IFN-alpha might have a role in directing Ig isotype selection. Consistent with this possibility, we have found that injection of mice with recombinant mouse IFN-alpha suppresses IgE secretion, enhances IgG2a secretion, and has no independent effect on IgG1 secretion in mice stimulated with a foreign anti-IgD antibody. Injection of mice with polyinosinic acid.polycytidylic acid (poly I.C), an inducer of macrophage IFN-alpha production, also suppresses the anti-IgD antibody-induced IgE response and stimulates the IgG2a response; these effects are blocked by a sheep antibody that neutralizes mouse IFN-alpha/beta. Both recombinant IFN-alpha and poly I.C have maximum IgE suppressive and IgG2a stimulatory effects when injected early in the anti-IgD antibody-induced immune response. Addition of IFN-alpha to mouse B cells cultured with lipopolysaccharide (LPS) + interleukin 4 (IL-4) suppresses both IgG1 and IgE production, but much less potently than IFN-gamma. IFN-alpha suppresses anti-IgD antibody-induced increases in the level of splenic IL-4 mRNA, but enhances the anti-IgD antibody-induced increase in the splenic level of IFN-gamma mRNA. These results are consistent with the effect of IFN-alpha on Ig isotype expression in mice, as IL-4 stimulates IgE and suppresses IgG2a secretion while IFN-gamma exerts opposite effects. These observations suggest that antigen presenting cells, by secreting IFN-alpha early in the course of an immune response, can influence the nature of that response both through direct effects on B cells and by influencing the differentiation of T cells.
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
F D
FD
Finkelman
A
A
Svetic
I
I
Gresser
C
C
Snapper
J
J
Holmes
P P
PP
Trotta
I M
IM
Katona
W C
WC
Gause
D000818:Animals; D005260:Female; D006041:Goats; D007072:Immunoglobulin D / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000276:immunology*; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins; D013154:Spleen / Q000187:drug effects
D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007370:Interferon Type I; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma