Class Switch Recombination and Somatic Hypermutation in Early Mouse B Cells Are Mediated by B Cell and Toll-like Receptors

Program in Immunology and Department of Pathology, Sackler School of Graduate Biomedical Sciences and Tufts University School of Medicine, Boston, MA 02111, USA.
Immunity (Impact Factor: 21.56). 08/2007; 27(1):64-75. DOI: 10.1016/j.immuni.2007.05.018
Source: PubMed


Activation-induced cytidine deaminase (AID) is required for immunoglobulin (Ig) gene class switch recombination (CSR), somatic hypermutation (SHM), and somatic hyperconversion. In general, high AID expression is found in mature B cells that are responding to antigens. However, AID expression and SHM have also been detected in developing B cells from transgenic mice that have a limited Ig repertoire. Here we demonstrate that AID expression, ongoing CSR, and active SHM occur in developing B cells from wild-type mice. Further, our results suggest that somatic variants arising from developing B cells in the bone marrow further diversify in the spleen of unimmunized mice. AID expression in developing B cells is T cell independent but involves engagement of B cell receptors and Toll-like receptors. Early AID expression can increase the preimmune repertoire of developing B cells, may provide an innate population of IgG- and IgA-expressing cells, and could be involved in receptor editing of self-reactive immature B cells.

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    • "Although physiological AID expression is largely restricted to mature B cells, its expression has also been reported in other settings. AID is expressed in developing B cells in the bone marrow, inducing robust CSR to a subset of isotypes (31, 32). The physiological relevance of CSR in the bone marrow is not clear at present. "
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    • "This ensures high AID expression only in activated B cells with appropriate signals, as occurring within GCs upon interaction with follicular dendritic cells and T follicular helper cells. In addition, AID can appear at low levels in some bone marrow developing B cells upon stimulation of toll like receptors (TLR) [7, 8]. "
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    • "T1 was somewhat higher compared with B6 T1 cells, but differences were not statistically significant (Fig. 4 F). Importantly, consistent with Ueda et al. (2007) and Han et al. (2007), T1 cells were the only B cell subset with measurable levels of Aicda mRNA, suggesting that unstimulated T1 cells have the capacity to produce class­switched Abs. Further analysis of TLR7.1Tg and WT T1, T2, FO, and MZ B cells revealed that TLR7.1Tg "
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