Cutting edge: IL-21 is a switch factor for the production of IgG1 and IgG3 by human B cells.
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).
Pène
Jérôme
J
Institut National de la Santé et de la Recherche Médicale, Unité 454, Montpellier, France.
Gauchat
Jean-François
JF
Lécart
Sandrine
S
Drouet
Elodie
E
Guglielmi
Paul
P
Boulay
Vera
V
Delwail
Adriana
A
Foster
Don
D
Lecron
Jean-Claude
JC
Yssel
Hans
H
D018941:Antigens, CD19 / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D019013:CD40 Antigens / Q000494:pharmacology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000096:biosynthesis; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000145:classification* / Q000235:genetics; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis* / Q000235:genetics; D007134:Immunoglobulin Switch Region; D007142:Immunoglobulin gamma-Chains / Q000096:biosynthesis / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis / Q000235:genetics; D007378:Interleukins / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology; D000098546:Interleukin-21; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D018941:Antigens, CD19; D019013:CD40 Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007142:Immunoglobulin gamma-Chains; D007148:Immunoglobulin mu-Chains; D007378:Interleukins; D007073:Immunoglobulin E; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase; D000098546:Interleukin-21