Oct2 enhances antibody-secreting cell differentiation through regulation of IL-5 receptor alpha chain expression on activated B cells

Emslie, D; D&#39;Costa, K; Hasbold, J; Metcalf, D; Takatsu, K; Hodgkin, PO; Corcoran, LM

Author(s): Emslie, D; D'Costa, K; Hasbold, J; Metcalf, D; Takatsu, K; Hodgkin, PO; Corcoran, LM;
Details: Publication Year 2008-02-18,Volume 205,Issue #2,Page 409-421
Journal Title: JOURNAL OF EXPERIMENTAL MEDICINE
Publication Type: Journal Article
Abstract: Mice lacking a functional gene for the Oct2 transcriptional activator display several developmental and functional deficiencies in the B lymphocyte lineage. These include defective B cell receptor (BCR) and Toll-like receptor 4 signaling, an absence of B-1 and marginal zone populations, and globally reduced levels of serum immunoglobulin (Ig) in naive and immunized animals. Oct2 was originally identified through its ability to bind to regulatory regions in the Ig loci, but genetic evidence has not supported an essential role for Oct2 in the expression of Ig genes. We describe a new Oct2-mediated role in B cells. Oct2 augments the ability of activated B cells to differentiate to antibody-secreting plasma cells (ASCs) under T cell-dependent conditions through direct regulation of the gene encoding the alpha chain of the interleukin (IL) 5 receptor. Ectopic expression of IL-5R alpha in oct2-deficient B cells largely restores their ability to differentiate to functional ASCs in vitro but does not correct other phenotypic defects in the mutants, such as the maturation and specialization of peripheral B cells, which must therefore rely on distinct Oct2 target genes. IL-5 augments ASC differentiation in vitro, and we show that IL-5 directly activates the plasma cell differentiation program by enhancing blimp1 expression.
Publisher: ROCKEFELLER UNIV PRESS
Link To PubMed Central Version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2271016/
Publisher's Version: https://doi.org/10.1084/jem.20072049
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2008-02-18 12:00:00

Last Modified: 2014-12-23 01:25:58