Oct2 enhances antibody-secreting cell differentiation through regulation of IL-5 receptor alpha chain expression on activated B cells.
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-5Ralpha 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.
Emslie
Dianne
D
Immunology Division, The Walter and Eliza Hall Institute, Parkville, Victoria 3050, Australia.
D'Costa
Kathy
K
Hasbold
Jhagvaral
J
Metcalf
Donald
D
Takatsu
Kiyoshi
K
Hodgkin
Philip O
PO
Corcoran
Lynn M
LM
D000818:Animals; D000921:Antibody-Producing Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D015848:Interleukin-5 / Q000494:pharmacology; D053666:Interleukin-5 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050813:Octamer Transcription Factor-2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
D015848:Interleukin-5; D053666:Interleukin-5 Receptor alpha Subunit; D050813:Octamer Transcription Factor-2; C513258:Prdm1 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C527275:interleukin-5- receptor alpha, mouse; D000074462:Positive Regulatory Domain I-Binding Factor 1