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Activation-induced cytidine deaminase expression and activity in the absence of germinal centers: insights into hyper-IgM syndrome.

Publication ,  Journal Article
Kuraoka, M; Liao, D; Yang, K; Allgood, SD; Levesque, MC; Kelsoe, G; Ueda, Y
Published in: J Immunol
September 1, 2009

Somatic hypermutation normally occurs as a consequence of the expression of activation-induced cytidine deaminase (AID) by Ag-activated, mature B cells during T cell-dependent germinal center responses. Nonetheless, despite their inability to express CD154 and initiate GC responses, patients with type 1 hyper-IgM syndrome (HIGM1) support populations of IgM(+)IgD(+)CD27(+) B cells that express mutated Ig genes. The origin of these mutated B cells is unknown; the IgM(+)IgD(+)CD27(+) cells do not express AID and appear to acquire mutations independent of stringent selection by Ag. Here, we demonstrate that immature/transitional 1 B cells from the bone marrow of CD154-deficient mice express AID and acquire Ig mutations that lack the hallmarks of antigenic selection via BCR signaling. Comparable levels of AID expression was found in developmentally immature B cells recovered from murine fetal liver and from human immature/transitional 1 B cells recovered from umbilical cord blood. AID expression in human fetal liver was also robust, approaching that of human tonsil tissue and the human germinal center B cell line, Ramos. These observations led us to conclude that AID expression in developing human B cells is the origin of the mutated IgM(+)IgD(+)CD27(+) B cells present in HIGM1 patients, and we propose that both mice and humans share a latent, AID-dependent pathway for the preimmune diversification of B lymphocytes that is more prominent in chicken, sheep, and rabbits.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

September 1, 2009

Volume

183

Issue

5

Start / End Page

3237 / 3248

Location

United States

Related Subject Headings

  • Stem Cells
  • Somatic Hypermutation, Immunoglobulin
  • Signal Transduction
  • Receptors, Antigen, B-Cell
  • Molecular Sequence Data
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Activation
  • Immunophenotyping
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kuraoka, M., Liao, D., Yang, K., Allgood, S. D., Levesque, M. C., Kelsoe, G., & Ueda, Y. (2009). Activation-induced cytidine deaminase expression and activity in the absence of germinal centers: insights into hyper-IgM syndrome. J Immunol, 183(5), 3237–3248. https://doi.org/10.4049/jimmunol.0901548
Kuraoka, Masayuki, Dongmei Liao, Kaiyong Yang, Sallie D. Allgood, Marc C. Levesque, Garnett Kelsoe, and Yoshihiro Ueda. “Activation-induced cytidine deaminase expression and activity in the absence of germinal centers: insights into hyper-IgM syndrome.J Immunol 183, no. 5 (September 1, 2009): 3237–48. https://doi.org/10.4049/jimmunol.0901548.
Kuraoka M, Liao D, Yang K, Allgood SD, Levesque MC, Kelsoe G, et al. Activation-induced cytidine deaminase expression and activity in the absence of germinal centers: insights into hyper-IgM syndrome. J Immunol. 2009 Sep 1;183(5):3237–48.
Kuraoka, Masayuki, et al. “Activation-induced cytidine deaminase expression and activity in the absence of germinal centers: insights into hyper-IgM syndrome.J Immunol, vol. 183, no. 5, Sept. 2009, pp. 3237–48. Pubmed, doi:10.4049/jimmunol.0901548.
Kuraoka M, Liao D, Yang K, Allgood SD, Levesque MC, Kelsoe G, Ueda Y. Activation-induced cytidine deaminase expression and activity in the absence of germinal centers: insights into hyper-IgM syndrome. J Immunol. 2009 Sep 1;183(5):3237–3248.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

September 1, 2009

Volume

183

Issue

5

Start / End Page

3237 / 3248

Location

United States

Related Subject Headings

  • Stem Cells
  • Somatic Hypermutation, Immunoglobulin
  • Signal Transduction
  • Receptors, Antigen, B-Cell
  • Molecular Sequence Data
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Activation
  • Immunophenotyping