Interleukin‐5 regulates genes involved in B‐cell terminal maturation

K Horikawa, K Takatsu - Immunology, 2006 - Wiley Online Library
Immunology, 2006Wiley Online Library
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 …
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.
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