1. ¹Division of Immunology and Genetics, John Curtin School of Medical Research, The Australian National University, Canberra, Australia
2. ²Australian National University Medical School, Canberra, Australia
3. ³Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, MD, USA
4. ⁴MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
5. ⁵Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA
6. ⁶Friedrich Miescher Institute, Basel, Switzerland
7. ⁷The Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA
8. ⁸Australian Phenomics Facility, Canberra, ACT, Australia

Correspondence: Dr CG Vinuesa, Division of Immunology and Genetics, John Curtin School of Medical Research, The Australian National University, Mills Road, PO Box 334, Canberra City, Australian Capital Territory 2601, Australia. E-mail: carola.vinuesa@anu.edu.au

Received 30 June 2007; Revised 30 August 2007; Accepted 2 September 2007; Published online 16 October 2007.

Abstract

Selection of B cells subjected to hypermutation in germinal centres (GC) during T cell-dependent (TD) antibody responses yields memory cells and long-lived plasma cells that produce high affinity antibodies biased to foreign antigens rather than self-antigens. GC also form in T-independent (TI) responses to polysaccharide antigens but failed selection results in GC involution and memory cells are not generated. To date there are no markers that allow phenotypic distinction of T-dependent and TI germinal centre B cells. We compared the global gene expression of GC B cells purified from mice immunized with either TD or TI antigens and identified eighty genes that are differentially expressed in TD GC. Significantly, the largest cluster comprises genes involved in growth and guidance of neuron axons such as Plexin B2, Basp1, Nelf, Shh, Sc4mol and Sult4. This is consistent with formation of long neurite (axon and dendrite)-like structures by mouse and human GC B cells, which may facilitate T:B cell interactions within GC, affinity maturation and B cell memory formation. Expression of BASP1 and PLEXIN B2 protein is very low or undetectable in resting and TI GC B cells, but markedly upregulated in GC B cells induced in the presence of T cell help. Finally we show some of the axon growth genes upregulated in TD-GC B cells including Basp1, Shh, Sult4, Sc4mol are also preferentially expressed in post-GC B cell neoplasms.