Novel role of the E26 transformation-specific transcription factor Spi-C for B cell development and function (IRM8P.703)

Transcription factors of the E26 transformation-specific family are critically important for regulating B cell development and function. Spi-B and Spi-C are highly related E26 transformation-specific transcription factors that can bind to identical DNA sequences in the genome. Spib-/- mice have reduced follicular and increased marginal zone B cell frequencies compared to WT mice. Spib-/- B cells are defective in BCR signaling, and cannot generate T-dependent antibody responses. Spi-C is expressed in developing B cells, but its function in B cell development and function is not clear. To determine if Spi-B and Spi-C are functionally redundant, we generated mice that are germline knockout for Spib and heterozygous for Spic (Spib-/-Spic+/-). Spib-/-Spic-/- mice were not born, potentially due to embryonic lethality. Interestingly, Spib-/-Spic+/- mice had restored number of B cells in the spleen, including a rescue of follicular B cells, and had restored proliferative responses compared to Spib-/- mice. Transcripts of genes important for BCR signaling were rescued in sorted follicular Spib-/-Spic+/- B cells compared to Spib-/- B cells. These results suggest a novel role for Spi-C in opposing Spi-B in B cell development and function. These findings have important implications for understanding antibody forming responses, such as those seen in vaccinations.