The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/2000/2/475/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 3, February 7, 2000 475-484

Original Article

bcl-2 Transgene Expression Inhibits Apoptosis in the Germinal Center and Reveals Differences in the Selection of Memory B Cells and Bone Marrow Antibody-Forming Cells

Kenneth G.C. Smithb, Amanda Lighta, Lorraine A. O'Reillya, Soon-Meng Anga, Andreas Strassera, and David Tarlintona

a The Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Victoria 3050, Australia
b Cambridge Institute for Medical Research and the Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 2QQ, United Kingdom
The Walter and Eliza Hall Institute, PO Royal Melbourne Hospital, Victoria 3050, Australia.61-3-9347-085261-3-9345-2615

tarlinton{at}wehi.edu.au

Immunization with T cell–dependent antigens generates long-lived memory B cells and antibody-forming cells (AFCs). Both populations originate in germinal centers and, predominantly, produce antibodies with high affinity for antigen. The means by which germinal center B cells are recruited into these populations remains unclear. We have examined affinity maturation of antigen-specific B cells in mice expressing the cell death inhibitor bcl-2 as a transgene. Such mice had reduced apoptosis in germinal centers and an excessive number of memory B cells with a low frequency of V gene somatic mutation, including those mutations encoding amino acid exchanges known to enhance affinity. Despite the frequency of AFCs being increased in bcl-2–transgenic mice, the fraction secreting high-affinity antibody in the bone marrow at day 42 remained unchanged compared with controls. The inability of BCL-2 to alter selection of bone marrow AFCs is consistent with these cells being selected within the germinal center on the basis of their affinity being above some threshold rather than their survival being due to a selective competition for an antigen-based signal. Continuous competition for antigen does, however, explain formation of the memory compartment.

Key Words: affinity maturation • B cell • immunologic memory • plasma cell • somatic mutation

Abbreviations used in this paper: AFC, antibody-forming cell; BCR, B cell antigen receptor; BrdU, bromodeoxyuridine; KLH, keyhole limpet hemocyanin; TUNEL, terminal deoxynucleotidyltransferase–mediated dUTP-biotin nick-end labeling.

© 2000 The Rockefeller University Press


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