Differential effect of IL-4 and IL-13 on the expression of recombination-activating genes in mature B cells from human peripheral blood.
We examined the expression of recombination-activating genes (RAG-1 and RAG-2) and activation-induced cytidine deaminase (AID) by mature human blood B cells stimulated with anti-CD40 in the presence of IL-4 or IL-13. IL-4 was an effective cofactor for RAG-1 and RAG-2 expression, whereas IL-13 was not. In addition, IL-4-dependent RAG expression combined with AID and IgE expression allowed predominant expression of newly rearranged lambda light chains on IgE+ cells generated from kappa+ cells. Although the magnitudes of IL-4- and IL-13-dependent AID and IgE expression were related to expression levels of binding subunits of the IL-4 and IL-13 receptors, IL-13 was ineffective for light chain replacement in the induced IgE+ cells due to the failure in RAG expression. Our studies using mature blood B cells indicate that IL-4-responsive cells, unlike IL-13-responsive cells, undergo lambda gene rearrangement leading to replacement in parallel with RAG expression and suggest that this replacement may contribute to the regulation of affinity maturation of IgE antibodies.
Kajiwara
Keiichi
K
Clinical Research Center, National Sagamihara Hospital, 18-1 Sakuradai, Sagamihara 228-8522, Japan.
Shinazawa
Miki
M
Morishima
Hirotaka
H
Yanagihara
Yukiyoshi
Y
D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D019013:CD40 Antigens / Q000502:physiology; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects*; D016654:Genes, RAG-1; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics; D016130:Immunophenotyping; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D009687:Nuclear Proteins; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D018793:Interleukin-13; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C064655:V(D)J recombination activating protein 2; D015847:Interleukin-4; D007073:Immunoglobulin E; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase