Class switch recombination and somatic hypermutation in early mouse B cells are mediated by B cell and Toll-like receptors.
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.
Han
Jin-Hwan
JH
Program in Immunology and Department of Pathology, Sackler School of Graduate Biomedical Sciences and Tufts University School of Medicine, Boston, MA 02111, USA.
Akira
Shizuo
S
Calame
Kathryn
K
Beutler
Bruce
B
Selsing
Erik
E
Imanishi-Kari
Thereza
T
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D003564:Cytidine Deaminase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008819:Mice, Nude; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D011995:Recombination, Genetic / Q000276:immunology*; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D051193:Toll-Like Receptors / Q000502:physiology*
D011947:Receptors, Antigen, B-Cell; D051193:Toll-Like Receptors; D003564:Cytidine Deaminase