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Interleukin‐5 regulates genes involved in B‐cell terminal maturation
Author(s) -
Horikawa Keisuke,
Takatsu Kiyoshi
Publication year - 2006
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02382.x
Subject(s) - immunoglobulin class switching , microbiology and biotechnology , biology , b cell , cd38 , antibody , cytidine deaminase , gene , immunology , stem cell , genetics , cd34
Summary Interleukin (IL)‐5 induces CD38‐activated splenic B cells to differentiate into immunoglobulin M‐secreting cells and undergo µ to γ1 class switch recombination (CSR) at the DNA level, resulting in immunoglobulin G1 (IgG1) production. Interestingly, IL‐4, a well‐known IgG1‐inducing factor does not induce immunoglobulin production or µ to γ1 CSR in CD38‐activated B cells. In the present study, we implemented complementary DNA microarrays to investigate the contribution of IL‐5‐induced gene expression in CD38‐stimulated B cells to immunoglobulin‐secreting cell differentiation and µ to γ1 CSR. IL‐5 and IL‐4 stimulation of CD38‐activated B cells induced the expression of 418 and 289 genes, respectively, that consisted of several clusters. Surprisingly, IL‐5‐inducible 78 genes were redundantly regulated by IL‐4. IL‐5 and IL‐4 also suppressed the gene expression of 319 and 325 genes, respectively, 97 of which were overlapped. Genes critically regulated by IL‐5 include immunoglobulin ‐related genes such as J chain and immunoglobulinκ , and genes involved in B‐cell maturation such as BCL6 , activation‐induced cytidine deaminase (Aid) and B lymphocyte‐induced maturation protein‐1 (Blimp‐1) and tend to be induced slowly after IL‐5 stimulation. Intriguingly, among genes, the retroviral induction of Blimp‐1 and Aid in CD38‐activated B cells could induce IL‐4‐dependent maturation to Syndecan‐1 + antibody‐secreting cells and µ to γ1 CSR, respectively, in CD38‐activated B cells. Taken together, preferential Aid and Blimp‐1 expression plays a critical role in IL‐5‐induced immunoglobulin‐secreting cell differentiation and µ to γ1 CSR in CD38‐activated B cells.