Transgenic expression of Spi-C impairs B-cell development and function by affecting genes associated with BCR signaling.
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 the function of Spi-C in B-cell development, we generated mice expressing a B-cell-specific Spi-C transgene under the control of the IgH intronic enhancer. Spi-C transgenic mice had 50% fewer B cells than wild-type littermates. Flow cytometric analyses showed that splenic transitional B cells and bone marrow pre-B or immature B cells from transgenic mice were dramatically reduced compared with those of wild type. Both nonspecific and Ag-specific serum IgM levels were significantly increased in transgenic mice, while serum IgG levels were significantly decreased compared with wild type. Spi-C transgenic B cells proliferated poorly after stimulation by anti-IgM or anti-CD40 in vitro, although they responded normally to LPS stimulation. Using real-time RT-PCR, we found that several BCR signaling-related mediators were downregulated at pre-B-cell and mature B-cell stages in transgenic mice, while an inhibitor of BCR signaling was upregulated. Taken together, these data indicate that ectopic expression of Spi-C can impair B-cell development and function by affecting genes associated with BCR signaling.
Zhu
Xiang
X
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0524, USA.
Schweitzer
Brock L
BL
Romer
Eric J
EJ
Sulentic
Courtney E W
CE
DeKoter
Rodney P
RP
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell; C423918:Spic protein, mouse
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