Transgenic expression of Spi-C impairs B-cell development and function by affecting genes associated with BCR signaling

Eur J Immunol. 2008 Sep;38(9):2587-99. doi: 10.1002/eji.200838323.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism*
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Lipopolysaccharides / immunology
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction


  • DNA-Binding Proteins
  • Immunoglobulin G
  • Immunoglobulin M
  • Lipopolysaccharides
  • Receptors, Antigen, B-Cell
  • Spic protein, mouse