TY - JOUR
T1 - Class Switch Recombination and Somatic Hypermutation in Early Mouse B Cells Are Mediated by B Cell and Toll-like Receptors
AU - Han, Jin Hwan
AU - Akira, Shizuo
AU - Calame, Kathryn
AU - Beutler, Bruce
AU - Selsing, Erik
AU - Imanishi-Kari, Thereza
N1 - Funding Information:
We would like to thank E. Kari and R. Berland for critical review of our manuscript. We also thank J. Stavnezer and A. Marshak-Rothstein for providing AID-deficient mice (J. Stavnezer) and MyD88-deficient and Unc93b1 3d/3d mice (A. Marshak-Rothstein) and for helpful discussions. We are grateful to L. Hu for MyD88-deficient mice as well. We also thank A. Parmelee, S. Kwok, C. Martin, and J. Bergerson for valuable assistance. We thank the Eshe Fund for their generous support. This work was supported by National Institutes of Health grants R01AI45104 (T.I.-K.), R01AI24465 (E.S.), R01AI43576 (K.C.), and R01GM060031 (B.B.) and Lupus Research Institute (T.I.-K.).
PY - 2007/7/27
Y1 - 2007/7/27
N2 - 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.
AB - 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.
KW - CELLIMMUNO
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=34447617375&partnerID=8YFLogxK
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U2 - 10.1016/j.immuni.2007.05.018
DO - 10.1016/j.immuni.2007.05.018
M3 - Article
C2 - 17658280
AN - SCOPUS:34447617375
SN - 1074-7613
VL - 27
SP - 64
EP - 75
JO - Immunity
JF - Immunity
IS - 1
ER -