The Journal of Experimental Medicine
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Published online 6 August 2001. doi:10.1084/jem.194.3.375
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© The Rockefeller University Press, 0022-1007/2001/8/375/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 3, August 6, 2001 375-378

Brief Definitive Report

Somatic Hypermutation Shapes the Antibody Repertoire of Memory B Cells in Humans

Eric Meffrea, Nadia Catalanc, Françoise Seltzc, Alain Fischerb,c, Michel C. Nussenzweiga, and Anne Durandyc
a Laboratory of Molecular Immunology, The Rockefeller University, Howard Hughes Medical Institute, New York, NY 10021
b Unite d'Immunologie-Hematologie, Hopital Necker-Enfants Malades, Paris 75015, France
c Institut National de la Santé et de la Recherche Médicale (INSERM) U429, Hopital Necker-Enfants Malades, Paris 75015, France

Correspondence to: Michel C. Nussenzweig, Department of Molecular Immunology, The Rockefeller University, RRB Rm. 470, Box 220, 1230 York Ave., New York, NY 10021. Tel:212-327-8106 Fax:212-327-8370 E-mail:nussen{at}mail.rockefeller.edu.

High-affinity antibodies produced by memory B cells differ from antibodies produced in naive B cells in two respects. First, many of these antibodies show somatic hypermutation, and second, the repertoire of antibodies expressed in memory responses is highly selected. To determine whether somatic hypermutation is responsible for the shift in the antibody repertoire during affinity maturation, we analyzed the immunoglobulin lambda light chain (Ig{lambda}) repertoire expressed by naive and antigen-selected memory B cells in humans. We found that the Ig{lambda} repertoire differs between naive and memory B cells and that this shift in the repertoire does not occur in the absence of somatic hypermutation in patients lacking activation-induced cytidine deaminase (AID). Our work suggests that somatic hypermutation makes a significant contribution to shaping the antigen-selected antibody repertoire in humans.

Key Words: immunoglobulin repertoire, activation-induced cytidine deaminase, somatic hypermutation, memory B cell, affinity maturation


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