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

Jin Hwan Han, Shizuo Akira, Kathryn Calame, Bruce Beutler, Erik Selsing, Thereza Imanishi-Kari

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)64-75
Number of pages12
JournalImmunity
Volume27
Issue number1
DOIs
StatePublished - Jul 27 2007

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Toll-Like Receptors
Genetic Recombination
B-Lymphocytes
Immunoglobulin Genes
B-Lymphoid Precursor Cells
Immunoglobulin Isotypes
Immunoglobulin A
Transgenic Mice
AICDA (activation-induced cytidine deaminase)
Immunoglobulins
Spleen
Immunoglobulin G
Bone Marrow
T-Lymphocytes
Antigens
Population

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Class Switch Recombination and Somatic Hypermutation in Early Mouse B Cells Are Mediated by B Cell and Toll-like Receptors. / Han, Jin Hwan; Akira, Shizuo; Calame, Kathryn; Beutler, Bruce; Selsing, Erik; Imanishi-Kari, Thereza.

In: Immunity, Vol. 27, No. 1, 27.07.2007, p. 64-75.

Research output: Contribution to journalArticle

Han, Jin Hwan ; Akira, Shizuo ; Calame, Kathryn ; Beutler, Bruce ; Selsing, Erik ; Imanishi-Kari, Thereza. / Class Switch Recombination and Somatic Hypermutation in Early Mouse B Cells Are Mediated by B Cell and Toll-like Receptors. In: Immunity. 2007 ; Vol. 27, No. 1. pp. 64-75.
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