Côrte-Real, JRodo, JoanaAlmeida, PCoutinho, AntónioDemengeot, JocelynePenha-Gonçalves, Carlos2010-05-142010-05-142009Côrte-Real, J., Rodo, J., Almeida, P., Garcia, J., Coutinho, A., Demengeot, J., Penha Gonçalves, C. (2009). Irf4 is a positional and functional candidate gene for the control of serum IgM levels in the mouse. Genes Immun 10(1) :1-71466-4879http://hdl.handle.net/10400.7/112Natural IgM are involved in numerous immunological functions but the genetic factors that control the homeostasis of its secretion and upholding remain unknown. Prompted by the finding that C57BL/6 mice had significantly lower serum levels of IgM when compared with BALB/c mice, we performed a genome-wide screen and found that the level of serum IgM was controlled by a QTL on chromosome 13 reaching the highest level of association at marker D13Mit266 (LOD score¼3.54). This locus was named IgMSC1 and covered a region encompassing the interferon-regulatory factor 4 gene (Irf4). The number of splenic mature B cells in C57BL/6 did not differ from BALB/c mice but we found that low serum levels of IgM in C57BL/6 mice correlated with lower frequency of IgM-secreting cells in the spleen and in the peritoneal cavity. These results suggested that C57BL/6 mice have lower efficiency in late B-cell maturation, a process that is highly impaired in Irf4 knockout mice. In fact, we also found reduced Irf4 gene expression in B cells of C57BL/6 mice. Thus, we propose Irf4 as a candidate for the IgMSC1 locus, which controls IgM homeostatic levels at the level of B-cell terminal differentiation.engSerum IgMhomeostasisIRF4journal article