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© The Rockefeller University Press, 0022-1007/2000/2/485/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 3, February 7, 2000 485-494

Original Article

Germinal Centers without T Cells

Carola García de Vinuesaa, Matthew C. Cooka, Jennifer Balla, Marion Drewa, Yvonne Sunnersa, Marilia Cascalhob, Matthias Wablb, Gerry G.B. Klausc, and Ian C.M. MacLennana

a From the Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, United Kingdom
b Department of Microbiology and Immunology, University of California, San Francisco, California 94103-0670
c Division of Cellular Immunology, National Institute for Medical Research, London NW7 1AA, United Kingdom
MRC/University of Birmingham Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, UK.44-121-414-359944-121-414-4068

i.c.m.maclennan{at}bham.ac.uk

Germinal centers are critical for affinity maturation of antibody (Ab) responses. This process allows the production of high-efficiency neutralizing Ab that protects against virus infection and bacterial exotoxins. In germinal centers, responding B cells selectively mutate the genes that encode their receptors for antigen. This process can change Ab affinity and specificity. The mutated cells that produce high-affinity Ab are selected to become Ab-forming or memory B cells, whereas cells that have lost affinity or acquired autoreactivity are eliminated. Normally, T cells are critical for germinal center formation and subsequent B cell selection. Both processes involve engagement of CD40 on B cells by T cells. This report describes how high-affinity B cells can be induced to form large germinal centers in response to (4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll in the absence of T cells or signaling through CD40 or CD28. This requires extensive cross-linking of the B cell receptors, and a frequency of antigen-specific B cells of at least 1 in 1,000. These germinal centers abort dramatically at the time when mutated high-affinity B cells are normally selected by T cells. Thus, there is a fail-safe mechanism against autoreactivity, even in the event of thymus-independent germinal center formation.

Key Words: quasimonoclonal mice • (4-hydroxy-3-nitrophenyl)acetyl–Ficoll • germinal centers • CD40 ligation • thymus independent

Abbreviations used in this paper: AP, alkaline phosphatase; BCR, B cell receptor; BrdU, 5-bromo-2'-deoxyuridine; CTLA-4, CTL antigen 4; H{gamma}1, human {gamma}1; NP, (4-hydroxy-3-nitrophenyl)acetyl; PNA, peanut agglutinin; QM, quasimonoclonal; TdT, terminal deoxynucleotidyltransferase; TUNEL, TdT-mediated dUTP nick end labeling.

© 2000 The Rockefeller University Press


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