Abstract
IL-21 is a cytokine that regulates the activation of T and NK cells and promotes the proliferation of B cells activated via CD40. In this study, we show that rIL-21 strongly induces the production of all IgG isotypes by purified CD19(+) human spleen or peripheral blood B cells stimulated with anti-CD40 mAb. Moreover, it was found to specifically induce the production of IgG(1) and IgG(3) by CD40-activated CD19(+)CD27(-) naive human B cells. Although stimulation of CD19(+) B cells via CD40 alone induced gamma 1 and gamma 3 germline transcripts, as well as the expression of activation-induced cytidine deaminase, only stimulation with both anti-CD40 mAb and rIL-21 resulted in the production of S gamma/S mu switch circular DNA. These results show that IL-21, in addition to promoting growth and differentiation of committed B cells, is a specific switch factor for the production of IgG(1) and IgG(3).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD19 / biosynthesis
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B-Lymphocyte Subsets / cytology
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B-Lymphocyte Subsets / immunology*
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B-Lymphocyte Subsets / metabolism*
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CD40 Antigens / pharmacology
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Cell Division / genetics
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Cell Division / immunology
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Cells, Cultured
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Cytidine Deaminase
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Cytosine Deaminase / biosynthesis
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Humans
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Immunoglobulin A / biosynthesis
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Immunoglobulin E / biosynthesis
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Immunoglobulin G / biosynthesis*
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Immunoglobulin G / classification*
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Immunoglobulin G / genetics
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Immunoglobulin Isotypes / biosynthesis*
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Immunoglobulin Isotypes / genetics
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Immunoglobulin Switch Region*
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Immunoglobulin gamma-Chains / biosynthesis
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Immunoglobulin gamma-Chains / genetics
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Immunoglobulin mu-Chains / biosynthesis
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Immunoglobulin mu-Chains / genetics
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Interleukins / physiology*
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Lymphocyte Activation / genetics
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Spleen / cytology
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Spleen / immunology
Substances
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Antigens, CD19
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CD40 Antigens
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Immunoglobulin A
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Immunoglobulin G
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Immunoglobulin Isotypes
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Immunoglobulin gamma-Chains
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Immunoglobulin mu-Chains
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Interleukins
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Immunoglobulin E
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AICDA (activation-induced cytidine deaminase)
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Cytosine Deaminase
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Cytidine Deaminase
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interleukin-21