Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas

Alberto Martin, Philip D. Bardwell, Caroline J. Woo, Manxia Fan, Marc J. Shulman, Matthew D. Scharff

Research output: Contribution to journalArticle

216 Citations (Scopus)

Abstract

The production of high-affinity protective antibodies requires somatic hypermutation (SHM) of the antibody variable (V)-region genes. SHM is characterized by a high frequency of point mutations that occur only during the centroblast stage of B-cell differentiation. Activation-induced cytidine deaminase (AID), which is expressed specifically in germinal-centre centroblasts, is required for this process, but its exact role is unknown. Here we show that AID is required for SHM in the centroblast-like Ramos cells, and that expression of AID is sufficient to induce SHM in hybridoma cells, which represent a later stage of B-cell differentiation that does not normally undergo SHM. In one hybridoma, mutations were exclusively in G-C base pairs that were mostly within RGYW or WRCY motifs, suggesting that AID has primary responsibility for mutations at these nucleotides. The activation of SHM in hybridomas indicates that AID does not require other centroblast-specific cofactors to induce SHM, suggesting either that it functions alone or that the factors it requires are expressed at other stages of B-cell differentiation.

Original languageEnglish (US)
Pages (from-to)802-806
Number of pages5
JournalNature
Volume415
Issue number6873
StatePublished - Feb 14 2002

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Hybridomas
Cell Differentiation
B-Lymphocytes
Mutation
Antibody Affinity
Germinal Center
Point Mutation
Base Pairing
Nucleotides
AICDA (activation-induced cytidine deaminase)
Antibodies
Genes

ASJC Scopus subject areas

  • General

Cite this

Martin, A., Bardwell, P. D., Woo, C. J., Fan, M., Shulman, M. J., & Scharff, M. D. (2002). Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas. Nature, 415(6873), 802-806.

Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas. / Martin, Alberto; Bardwell, Philip D.; Woo, Caroline J.; Fan, Manxia; Shulman, Marc J.; Scharff, Matthew D.

In: Nature, Vol. 415, No. 6873, 14.02.2002, p. 802-806.

Research output: Contribution to journalArticle

Martin, A, Bardwell, PD, Woo, CJ, Fan, M, Shulman, MJ & Scharff, MD 2002, 'Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas', Nature, vol. 415, no. 6873, pp. 802-806.
Martin A, Bardwell PD, Woo CJ, Fan M, Shulman MJ, Scharff MD. Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas. Nature. 2002 Feb 14;415(6873):802-806.
Martin, Alberto ; Bardwell, Philip D. ; Woo, Caroline J. ; Fan, Manxia ; Shulman, Marc J. ; Scharff, Matthew D. / Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas. In: Nature. 2002 ; Vol. 415, No. 6873. pp. 802-806.
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