Abstract
Growing evidence indicates that B cells are not the only source of immunoglobulin (Ig). To investigate this discovery further, we used μMT mice, which have a disruption of the first transmembrane exon of the μ heavy chain and do not express the membrane form of IgM. These mice lack mature B cells and thus serve as a good model to explore Ig expression by liver epithelial cells. We found that Ig heavy chains (μ, δ, γ and α) and light chains (κ and λ) were expressed in sorted liver epithelial cells of μMT mice. Surprisingly, each heavy chain class showed its respective variable region sequence characteristics in their variable region, instead of sharing the same VDJ usage, which suggests that class switching does not occur in liver epithelial cells. Moreover, the γ and α chains, but not the μ and δ chains, showed mutations in the variable region, thus indicating that different classes of Ig have different activities. Our findings support the concept that non-B cells, liver epithelial cells here, can produce different classes of Ig.
Highlights
Immunoglobulin (Ig) is one of the classic immune molecules and plays an important role in the body’s immune response
By using B cell-deficient μMT mice, we further provided evidence that Ig can be expressed by non-B cells under physiological conditions
We found that liver epithelial cells produced multiple classes of Ig, including IgG, IgM, IgA and IgD
Summary
Immunoglobulin (Ig) is one of the classic immune molecules and plays an important role in the body’s immune response. Normal epithelial cell-derived IgG, IgA and IgM showed characteristic antibody activity[9,22] All of these studies have challenged the classical concept that B cells are the only source of Ig. The functional membrane form of the IgM heavy chain (μ) is thought to be essential for B cell differentiation. The B cell-deficient μMT mice contain a disruption of the first transmembrane exon of the μ heavy chain and do not express the membrane form of IgM. These mice lack mature B cells due to a developmental block at the pro-B cell stage, after which B cells undergo apoptosis. The liver epithelial cell-derived Ig transcripts displayed distinct characteristics compared with B cell-derived Ig transcripts
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