1. ¹Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
2. ²Centenary Institute of Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia
3. ³Faculty of Medicine, University of Sydney, Camperdown, New South Wales, Australia

Correspondence: Dr R Brink, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia. E-mail: r.brink@garvan.org.au

⁴Current address: Department of Microbiology and Immunology, University of California at San Francisco, 513 Parnassus Avenue, Box 0414, San Francisco, CA 94143, USA.

⁵Current address: Affitech AS, Oslo Research Park, Gaustadalléen 21, Oslo N-0349, Norway.

Received 12 October 2007; Accepted 13 October 2007; Published online 20 November 2007.

Abstract

Burnet's original description of the clonal selection hypothesis of antibody production included many prescient predictions of how 'lymphocytes carrying reactive sites' for foreign antigens might respond during immune responses. Somatic mutation, plasma cell differentiation and transition into memory cells were all described as potential fates for the 'variety of descendents' derived from proliferative expansion of antigen-reactive clones. After 50 years much is known about the molecular controls that drive these various processes. Comparatively little insight has been gained, however, into why particular daughter cells progress down one response pathway versus another. In this article, we briefly describe the evolution of the genetic technologies that now allow us to visualize the very processes predicted by Burnet. An in-depth description of the recently developed SW_HEL mouse model and its utility for tracking in vivo B-cell responses to various forms of hen-egg lysozyme (HEL) is also provided. Recent data obtained with this system indicate that antigen-dependent variables play a critical role in regulating the differentiation of responding B cells into antibody-secreting plasma cells.