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Ectopic Expression of Spi‐C Impairs B Cell Development and Function
Author(s) -
DeKoter Rodney P,
Schweitzer Brock L,
Romer Eric J,
Sulentic Courtney E. W.,
Zhu Xiang
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.345
Subject(s) - transgene , b cell , biology , ectopic expression , microbiology and biotechnology , genetically modified mouse , breakpoint cluster region , cd40 , enhancer , b cell receptor , antibody , receptor , gene expression , in vitro , gene , immunology , genetics , cytotoxic t cell
Spi‐C is an Ets family transcription factor closely related to PU.1 and Spi‐B. Expression of Spi‐C is developmentally regulated in the B cell lineage, but its function remains unknown. To determine potential functions for Spi‐C in B cell development, we generated mice expressing a Spi‐C transgene under control of the IgH intronic enhancer. Eμ‐Spi‐C transgenic mice had 50% fewer B cells than wild type littermates. Flow cytometric analysis showed a dramatic reduction of pre‐B and immature B cells in the bone marrow, and transitional B cells in the spleen of transgenic mice. Serum IgM levels in transgenic mice were significantly increased, while serum IgG levels were significantly decreased compared to wild type. Moreover, antigen‐specific IgM responses were also significantly increased in transgenic mice, while antigen‐specific IgG responses were decreased. Spi‐C transgenic B cells proliferated poorly and died in response to stimulation by anti‐IgM or anti‐CD40 antibody in vitro . Analysis of gene expression in Spi‐C transgenic B cells revealed a pattern of changes that account for reduced B cell receptor (BCR) signaling. Taken together, these data suggest that ectopic expression of Spi‐C impairs B cell development by altering expression of genes required for appropriate BCR signal transduction.