The Journal of Experimental Medicine
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Published online 9 October 2006 doi:10.1084/jem.20061254
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 11, 2419-2424
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BRIEF DEFINITIVE REPORT

 High affinity germinal center B cells are actively selected into the plasma cell compartment

Tri Giang Phan1,2, Didrik Paus1,2, Tyani D. Chan1,2, Marian L. Turner3, Stephen L. Nutt3, Antony Basten1,2, and Robert Brink1,2

1 Centenary Institute of Cancer Medicine and Cell Biology, Newtown NSW 2042, Australia
2 Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia
3 Walter and Eliza Hall Institute for Medical Research, Parkville VIC 3050, Australia

CORRESPONDENCE Robert Brink: r.brink{at}garvan.org.au.

A hallmark of T cell–dependent immune responses is the progressive increase in the ability of serum antibodies to bind antigen and provide immune protection. Affinity maturation of the antibody response is thought to be connected with the preferential survival of germinal centre (GC) B cells that have acquired increased affinity for antigen via somatic hypermutation of their immunoglobulin genes. However, the mechanisms that drive affinity maturation remain obscure because of the difficulty in tracking the affinity-based selection of GC B cells and their differentiation into plasma cells. We describe a powerful new model that allows these processes to be followed as they occur in vivo. In contrast to evidence from in vitro systems, responding GC B cells do not undergo plasma cell differentiation stochastically. Rather, only GC B cells that have acquired high affinity for the immunizing antigen form plasma cells. Affinity maturation is therefore driven by a tightly controlled mechanism that ensures only antibodies with the greatest possibility of neutralizing foreign antigen are produced. Because the body can sustain only limited numbers of plasma cells, this "quality control" over plasma cell differentiation is likely critical for establishing effective humoral immunity.

T.G. Phan and D. Paus contributed equally to this work.

T.G. Phan's present address is Dept. of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143.


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