Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells.
Recently the cDNA encoding interleukin 13 (IL-13), a T-cell-derived cytokine, was cloned and expressed. The present study demonstrates that IL-13 induces IgG4 and IgE synthesis by human B cells. IL-13-induced IgG4 and IgE synthesis by unfractionated peripheral blood mononuclear cells and highly purified B cells cultured in the presence of activated CD4+ T cells or their membranes. IL-13-induced IgG4 and IgE synthesis is IL-4-independent, since it was not affected by neutralizing anti-IL-4 monoclonal antibody. Highly purified, surface IgD+ B cells could also be induced to produce IgG4 and IgE by IL-13, indicating that the production of these isotypes reflected IgG4 and IgE switching and not a selective outgrowth of committed B cells. IL-4 and IL-13 added together at optimal concentrations had no additive or synergistic effect, suggesting that common signaling pathways may be involved. This notion is supported by the observation that IL-13, like IL-4, induced CD23 expression on B cells and enhanced CD72, surface IgM, and class II major histocompatibility complex antigen expression. In addition, like IL-4, IL-13 induced germ-line IgE heavy-chain gene transcription in highly purified B cells. Collectively, our data indicate that IL-13 is another T-cell-derived cytokine that, in addition to IL-4, efficiently directs naive human B cells to switch to IgG4 and IgE production.
Punnonen
J
J
Human Immunology Department, DNAX Research Institute, Palo Alto, CA 94304-1104.
Aversa
G
G
Cocks
B G
BG
McKenzie
A N
AN
Menon
S
S
Zurawski
G
G
de Waal Malefyt
R
R
de Vries
J E
JE
D000911:Antibodies, Monoclonal; D000917:Antibody Formation / Q000187:drug effects*; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000145:classification; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000145:classification; D007132:Immunoglobulin Isotypes / Q000032:analysis / Q000096:biosynthesis; D007139:Immunoglobulin epsilon-Chains / Q000096:biosynthesis / Q000235:genetics; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13; D015847:Interleukin-4 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology*; D010641:Phenotype; D017455:Receptors, IgE / Q000032:analysis / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007139:Immunoglobulin epsilon-Chains; D007370:Interferon Type I; D018793:Interleukin-13; D007378:Interleukins; D017455:Receptors, IgE; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma