97 research outputs found
Irf4 is a positional and functional candidate gene for the control of serum IgM levels in the mouse
Natural 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
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