The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20072049
The Journal of Experimental Medicine, Vol. 205, No. 2, 409-421
The Rockefeller University Press, 0022-1007 $30.00
© Emslie et al.
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ARTICLE

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

Dianne Emslie1, Kathy D'Costa1, Jhagvaral Hasbold1, Donald Metcalf2, Kiyoshi Takatsu3, Philip O. Hodgkin1, and Lynn M. Corcoran1

1 Immunology Division and 2 Division of Cancer and Haematology, The Walter and Eliza Hall Institute, Parkville, Victoria 3050, Australia
3 Division of Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

CORRESPONDENCE Lynn M. Corcoran: corcoran{at}wehi.edu.au

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.


Abbreviations used: ASC, antibody-secreting plasma cell; cDNA, complementary DNA; ChIP, chromatin immunoprecipitation; CHX, cycloheximide; ER, estrogen receptor; Hmbs, hydroxymethylbilane synthase; IRF, IFN regulatory factor; MZ, marginal zone; OBF, Oct binding factor; RACE, rapid amplification of cDNA ends; TD, T cell dependent; TI, T cell independent; TLR, Toll-like receptor.

D. Emslie and K. D'Costa contributed equally to this work.


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