In vivo control of B-cell survival and antigen-specific B-cell responses

Tyani D Chan, Sandra Gardam, Dominique Gatto, Vivian M Turner, John Silke, Robert Brink

Research output: Contribution to journalArticlepeer-review

Abstract

Targeted modification of the mouse genome provides the capability to manipulate complex physiological processes in a precise and controlled manner. Investigation of B-lymphocyte biology has benefited not only from the targeted modification of genes controlling B-cell survival and responsiveness, but also from the manipulation of antigen specificity made possible by targeting endogenous immunoglobulin loci. In this review, we discuss recent results obtained from our laboratory using gene-targeted mouse models to investigate the in vivo regulation of B-cell survival and responsiveness. The control of BAFF-dependent survival signals by the TRAF2- and TRAF3-signaling proteins is discussed as is the potential involvement of these molecules in B-lineage malignancies. We also outline the development and use of the SW(HEL) model for analyzing antigen-specific B-cell responses in vivo. This includes insights into the control of early decision-making during T-dependent B-cell differentiation, the affinity maturation and plasma cell differentiation of germinal center B cells, and the identification of EBI2 as a key regulator of B-cell migration and differentiation.

Original languageEnglish
Pages (from-to)90-103
Number of pages14
JournalImmunological reviews
Volume237
Issue number1
DOIs
Publication statusPublished - Sep 2010
Externally publishedYes

Keywords

  • Animals
  • B-Lymphocytes
  • Cell Survival
  • Germinal Center
  • Mice
  • Models, Immunological
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 3

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