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


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 signalling proteins is discussed as is the potential involvement of these molecules in B-lineage malignancies. We also outline the development and use of the SWHEL model for analysing 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.

Type Journal
ISBN 1600-065X (Electronic) 0105-2896 (Linking)
Authors Chan, T. D.; Gardam, S.; Gatto, D.; Turner, V. M.; Silke, J.; Brink, R.:
Responsible Garvan Author Tyani Chan
Published Date 2010-08-19
Published Volume 237
Published Issue 1
Published Pages 90-103
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version