The Journal of Experimental Medicine
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Published 4 February 2002. doi:10.1084/jem.20011112
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© Rockefeller University Press, 0022-1007/2002/2/383/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 3, February 4, 2002 383-389

Brief Definitive Report

Low-level Hypermutation in T Cell–independent Germinal Centers Compared with High Mutation Rates Associated with T Cell–dependent Germinal Centers

Kai-Michael Toellner, William E. Jenkinson, Dale R. Taylor, Mahmood Khan, Daniel M.-Y. Sze, David M. Sansom, Carola G. Vinuesa and Ian C.M. MacLennan

Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham B15 2TT, United Kingdom

Address correspondence to Professor Ian C.M. MacLennan, MRC Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, United Kingdom. Phone: 44-121-414-4068; Fax: 44-121-414-3599; E-mail: i.c.m.maclennan{at}bham.ac.uk

Exceptionally germinal center formation can be induced without T cell help by polysaccharide-based antigens, but these germinal centers involute by massive B cell apoptosis at the time centrocyte selection starts. This study investigates whether B cells in germinal centers induced by the T cell–independent antigen (4-hydroxy-3-nitrophenyl)acetyl (NP) conjugated to Ficoll undergo hypermutation in their immunoglobulin V region genes. Positive controls are provided by comparing germinal centers at the same stage of development in carrier-primed mice immunized with a T cell–dependent antigen: NP protein conjugate. False positive results from background germinal centers and false negatives from non-B cells in germinal centers were avoided by transferring B cells with a transgenic B cell receptor into congenic controls not carrying the transgene. By 4 d after immunization, hypermutation was well advanced in the T cell–dependent germinal centers. By contrast, the mutation rate for T cell–independent germinal centers was low, but significantly higher than in NP-specific B cells from nonimmunized transgenic mice. Interestingly, a similar rate of mutation was seen in extrafollicular plasma cells at this stage. It is concluded that efficient activation of hypermutation depends on interaction with T cells, but some hypermutation may be induced without such signals, even outside germinal centers.

Key Words: spleen • plasma cells • DNA mutational analysis • adoptive cell transfer • immunization


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